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183 results on '"Jiménez Vacas, Juan M."'

1. Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target

Author

Montero-Hidalgo, Antonio J., Gómez-Gómez, Enrique, Galán-Cañete, Manuel, Porcel-Pastrana, Francisco, Pérez-Gómez, Jesús M., Ortega-Bellido, María, Carrasco-Valiente, Julia, Chamorro-Castillo, Laura, Campos-Hernández, Juan P., Rangel-Zuñiga, Oriol A., González-Serrano, Teresa, Sánchez-Sánchez, Rafael, Sarmento-Cabral, André, Gahete, Manuel D., Jiménez-Vacas, Juan M., and Luque, Raúl M.

Published
2024
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2. SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances

Author

Fuentes-Fayos, Antonio C, Pérez-Gómez, Jesús M, G-García, Miguel E, Jiménez-Vacas, Juan M, Blanco-Acevedo, Cristóbal, Sánchez-Sánchez, Rafael, Solivera, Juan, Breunig, Joshua J, Gahete, Manuel D, Castaño, Justo P, and Luque, Raúl M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Rare Diseases, Brain Disorders, Neurosciences, Brain Cancer, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Apoptosis, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Glioblastoma, Humans, Mice, Phosphoproteins, RNA Splicing Factors, Survival Analysis, TOR Serine-Threonine Kinases, Transfection, Xenograft Model Antitumor Assays, bcl-X Protein, beta Catenin, Splicing factor SF3B1, Glioma mouse models, Antitumor therapy, BCL2L1 splicing variants, Oncology and carcinogenesis
Abstract

BackgroundGlioblastoma is one of the most devastating cancer worldwide based on its locally aggressive behavior and because it cannot be cured by current therapies. Defects in alternative splicing process are frequent in cancer. Recently, we demonstrated that dysregulation of the spliceosome is directly associated with glioma development, progression, and aggressiveness.MethodsDifferent human cohorts and a dataset from different glioma mouse models were analyzed to determine the mutation frequency as well as the gene and protein expression levels between tumor and control samples of the splicing-factor-3B-subunit-1 (SF3B1), an essential and druggable spliceosome component. SF3B1 expression was also explored at the single-cell level across all cell subpopulations and transcriptomic programs. The association of SF3B1 expression with relevant clinical data (e.g., overall survival) in different human cohorts was also analyzed. Different functional (proliferation/migration/tumorspheres and colonies formation/VEGF secretion/apoptosis) and mechanistic (gene expression/signaling pathways) assays were performed in three different glioblastomas cell models (human primary cultures and cell lines) in response to SF3B1 blockade (using pladienolide B treatment). Moreover, tumor progression and formation were monitored in response to SF3B1 blockade in two preclinical xenograft glioblastoma mouse models.ResultsOur data provide novel evidence demonstrating that the splicing-factor-3B-subunit-1 (SF3B1, an essential and druggable spliceosome component) is low-frequency mutated in human gliomas (~ 1 %) but widely overexpressed in glioblastoma compared with control samples from the different human cohorts and mouse models included in the present study, wherein SF3B1 levels are associated with key molecular and clinical features (e.g., overall survival, poor prognosis and/or drug resistance). Remarkably, in vitro and in vivo blockade of SF3B1 activity with pladienolide B drastically altered multiple glioblastoma pathophysiological processes (i.e., reduction in proliferation, migration, tumorspheres formation, VEGF secretion, tumor initiation and increased apoptosis) likely by suppressing AKT/mTOR/ß-catenin pathways, and an imbalance of BCL2L1 splicing.ConclusionsTogether, we highlight SF3B1 as a potential diagnostic and prognostic biomarker and an efficient pharmacological target in glioblastoma, offering a clinically relevant opportunity worth to be explored in humans.

Published
2022

4. Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3

Author

Fuentes-Fayos, Antonio C, Vázquez-Borrego, Mari C, Jiménez-Vacas, Juan M, Bejarano, Leire, Pedraza-Arévalo, Sergio, L-López, Fernando, Blanco-Acevedo, Cristóbal, Sánchez-Sánchez, Rafael, Reyes, Oscar, Ventura, Sebastián, Solivera, Juan, Breunig, Joshua J, Blasco, María A, Gahete, Manuel D, Castaño, Justo P, and Luque, Raúl M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Neurosciences, Genetics, Brain Cancer, Rare Diseases, Brain Disorders, Cancer, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, 2.1 Biological and endogenous factors, Alternative Splicing, Apoptosis, Biomarkers, Tumor, Brain Neoplasms, Cell Movement, Cell Proliferation, Gene Expression Regulation, Neoplastic, Gene Silencing, Glioblastoma, Humans, Neoplasm Invasiveness, Receptor, Platelet-Derived Growth Factor beta, Serine-Arginine Splicing Factors, Signal Transduction, Survival Analysis, Xenograft Model Antitumor Assays, glioblastoma, splicing machinery, SRSF3, PDGFRB pathway, antitumour therapy, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Glioblastomas remain the deadliest brain tumour, with a dismal ∼12-16-month survival from diagnosis. Therefore, identification of new diagnostic, prognostic and therapeutic tools to tackle glioblastomas is urgently needed. Emerging evidence indicates that the cellular machinery controlling the splicing process (spliceosome) is altered in tumours, leading to oncogenic splicing events associated with tumour progression and aggressiveness. Here, we identify for the first time a profound dysregulation in the expression of relevant spliceosome components and splicing factors (at mRNA and protein levels) in well characterized cohorts of human high-grade astrocytomas, mostly glioblastomas, compared to healthy brain control samples, being SRSF3, RBM22, PTBP1 and RBM3 able to perfectly discriminate between tumours and control samples, and between proneural-like or mesenchymal-like tumours versus control samples from different mouse models with gliomas. Results were confirmed in four additional and independent human cohorts. Silencing of SRSF3, RBM22, PTBP1 and RBM3 decreased aggressiveness parameters in vitro (e.g. proliferation, migration, tumorsphere-formation, etc.) and induced apoptosis, especially SRSF3. Remarkably, SRSF3 was correlated with patient survival and relevant tumour markers, and its silencing in vivo drastically decreased tumour development and progression, likely through a molecular/cellular mechanism involving PDGFRB and associated oncogenic signalling pathways (PI3K-AKT/ERK), which may also involve the distinct alteration of alternative splicing events of specific transcription factors controlling PDGFRB (i.e. TP73). Altogether, our results demonstrate a drastic splicing machinery-associated molecular dysregulation in glioblastomas, which could potentially be considered as a source of novel diagnostic and prognostic biomarkers as well as therapeutic targets for glioblastomas. Remarkably, SRSF3 is directly associated with glioblastoma development, progression, aggressiveness and patient survival and represents a novel potential therapeutic target to tackle this devastating pathology.

Published
2020

5. Metformin and simvastatin exert additive antitumour effects in glioblastoma via senescence-state: clinical and translational evidence

Author

Fuentes-Fayos, Antonio C., G-García, Miguel E., Pérez-Gómez, Jesús M., Montero-Hidalgo, Antonio J., Martín-Colom, Julia, Doval-Rosa, Carlos, Blanco-Acevedo, Cristóbal, Torres, Encarnación, Toledano-Delgado, Álvaro, Sánchez-Sánchez, Rafael, Peralbo-Santaella, Esther, Ortega-Salas, Rosa M., Jiménez-Vacas, Juan M., Tena-Sempere, Manuel, López, Miguel, Castaño, Justo P., Gahete, Manuel D., Solivera, Juan, and Luque, Raúl M.

Published
2023
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6. Tumor suppressor role of RBM22 in prostate cancer acting as a dual-factor regulating alternative splicing and transcription of key oncogenic genes

Author

Jiménez-Vacas, Juan M., Montero-Hidalgo, Antonio J., Gómez-Gómez, Enrique, Sáez-Martínez, Prudencio, Fuentes-Fayos, Antonio C., Closa, Adrià, González-Serrano, Teresa, Martínez-López, Ana, Sánchez-Sánchez, Rafael, López-Casas, Pedro P., Sarmento-Cabral, André, Olmos, David, Eyras, Eduardo, Castaño, Justo P., Gahete, Manuel D., and Luque, Raul M.

Published
2023
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7. Physiology of the Pituitary Hormone Secretion

Author

Fuentes-Fayos, Antonio C., Alors-Perez, Emilia, Jiménez-Vacas, Juan M., Herrero-Aguayo, Vicente, Sáez-Martínez, Prudencio, Lopez-Cánovas, Juan L., Vázquez-Borrego, María C., Castaño, Justo P., Kineman, Rhonda D., Gahete, Manuel D., Luque, Raúl M., Tamagno, Gianluca, editor, and Gahete, Manuel D., editor

Published
2022
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8. Spliceosomic dysregulation unveils NOVA1 as a candidate actionable therapeutic target in pancreatic neuroendocrine tumors

Author

Pedraza-Arevalo, Sergio, Alors-Pérez, Emilia, Blázquez-Encinas, Ricardo, Herrera-Martínez, Aura D., Jiménez-Vacas, Juan M., Fuentes-Fayos, Antonio C., Reyes, Óscar, Ventura, Sebastián, Sánchez-Sánchez, Rafael, Ortega-Salas, Rosa, Serrano-Blanch, Raquel, Gálvez-Moreno, María A., Gahete, Manuel D., Ibáñez-Costa, Alejandro, Luque, Raúl M., and Castaño, Justo P.

Published
2023
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9. The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.

Author

Hermán-Sánchez, Natalia, G-García, Miguel E., Jiménez-Vacas, Juan M., Yubero-Serrano, Elena M., López-Sánchez, Laura M., Romero-Martín, Sara, Raya-Povedano, Jose L., Álvarez-Benito, Marina, Castaño, Justo P., Luque, Raúl M., and Gahete, Manuel D.

Subjects
MEDICAL sciences, HORMONE receptors, OVERALL survival, BREAST cancer, CELL lines, RNA splicing, BREAST
Abstract

Breast cancer (BCa) is a highly prevalent pathological condition (̴30% in women) with limited and subtype-dependent prognosis and therapeutic options. Therefore, BCa management might benefit from the identification of novel molecular elements with clinical potential. Since splicing process is gaining a great relevance in cancer, this work analysed the expression of multiple Spliceosome Components (SCs = 17) and Splicing Factors (SFs = 26) and found a drastic dysregulation in BCa (n = 69) vs. control (negative biopsies; n = 50) samples. Among all the components analysed, we highlight the upregulation of ESRP1 and down-regulation of PRPF8 and NOVA1 in BCa vs. control samples. Indeed, ESRP1 was specially overexpressed in triple-negative BCa (TNBCa) and associated with worse prognosis (i.e., higher BCa grade and lower overall survival), suggesting an association of ESRP1 with BCa aggressiveness. On the other hand, PRPF8 expression was generally downregulated in BCa with no associations to clinical characteristics, while NOVA1 expression was lower in TNBCa patients and highly aggressive tumours. Consistently, NOVA1 overexpression in vitro reduced functional parameters of aggressiveness in ER-/PR- cell lines (MDA-MB-231 and BT-549) but not in ER+/PR+ cells (MCF7), suggesting a critical role of NOVA1 in subtype-specific BCa. Finally, the in vitro pharmacological inhibition of splicing machinery using pladienolide B decreased aggressiveness features in all the BCa cell lines, showing a subtype-independent inhibitory potential, but being relatively innocuous in normal-like breast cells. These results demonstrate the profound dysregulation of the splicing machinery in BCa and their potential as source of promising diagnosis/prognosis markers, as well as valuable therapeutic targets for BCa. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool

Author

Herrero-Aguayo, Vicente, Sáez-Martínez, Prudencio, Jiménez-Vacas, Juan M., Moreno-Montilla, M. Trinidad, Montero-Hidalgo, Antonio J., Pérez-Gómez, Jesús M., López-Canovas, Juan L., Porcel-Pastrana, Francisco, Carrasco-Valiente, Julia, Anglada, Francisco J., Gómez-Gómez, Enrique, Yubero-Serrano, Elena M., Ibañez-Costa, Alejandro, Herrera-Martínez, Aura D., Sarmento-Cabral, André, Gahete, Manuel D., and Luque, Raúl M.

Published
2022
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11. Supplementary Figure 7 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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12. Supplementary Figure 12 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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13. Data from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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14. Supplementary Figure 3 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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15. Supplementary Figure 2 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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16. Supplementary Table 5 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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17. Supplementary Figure 9 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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18. Supplementary Table 6 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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19. Supplementary Table 1 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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20. Supplementary Table 3 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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21. Supplementary Figure 8 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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22. Supplementary Materials and Methods from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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23. Supplementary Figure 5 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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24. Supplementary Figure 6 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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25. Supplementary Table 7 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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26. Supplementary Table 4 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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27. Supplementary Table 2 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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28. Supplementary Figure 4 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer

Author

Neeb, Antje, primary, Figueiredo, Ines, primary, Bogdan, Denisa, primary, Cato, Laura, primary, Stober, Jutta, primary, Jiménez-Vacas, Juan M., primary, Gourain, Victor, primary, Lee, Irene I., primary, Seeger, Rebecca, primary, Muhle-Goll, Claudia, primary, Gurel, Bora, primary, Welti, Jonathan, primary, Nava Rodrigues, Daniel, primary, Rekowski, Jan, primary, Qiu, Xintao, primary, Jiang, Yija, primary, Di Micco, Patrizio, primary, Mateos, Borja, primary, Bielskutė, Stasė, primary, Riisnaes, Ruth, primary, Ferreira, Ana, primary, Miranda, Susana, primary, Crespo, Mateus, primary, Buroni, Lorenzo, primary, Ning, Jian, primary, Carreira, Suzanne, primary, Bräse, Stefan, primary, Jung, Nicole, primary, Gräßle, Simone, primary, Swain, Amanda, primary, Salvatella, Xavier, primary, Plymate, Stephen R., primary, Al-Lazikani, Bissan, primary, Long, Henry W., primary, Yuan, Wei, primary, Brown, Myles, primary, Cato, Andrew C.B., primary, de Bono, Johann S., primary, and Sharp, Adam, primary

Published
2024
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30. Splicing factor SF3B1 is overexpressed and implicated in the aggressiveness and survival of hepatocellular carcinoma

Author

López-Cánovas, Juan L., del Rio-Moreno, Mercedes, García-Fernandez, Helena, Jiménez-Vacas, Juan M., Moreno-Montilla, M.Trinidad, Sánchez-Frias, Marina E., Amado, Víctor, L-López, Fernando, Fondevila, Marcos F., Ciria, Rubén, Gómez-Luque, Irene, Briceño, Javier, Nogueiras, Rubén, de la Mata, Manuel, Castaño, Justo P., Rodriguez-Perálvarez, Manuel, Luque, Raúl M., and Gahete, Manuel D.

Published
2021
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31. SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.

Author

Montero-Hidalgo, Antonio J., Jiménez-Vacas, Juan M., Gómez-Gómez, Enrique, Porcel-Pastrana, Francisco, Sáez-Martínez, Prudencio, Pérez-Gómez, Jesús M., Fuentes-Fayos, Antonio C., Blázquez-Encinas, Ricardo, Sánchez-Sánchez, Rafael, González-Serrano, Teresa, Castro, Elena, López-Soto, Pablo J., Carrasco-Valiente, Julia, Sarmento-Cabral, André, Martinez-Fuentes, Antonio J., Eyras, Eduardo, Castaño, Justo P., Sharp, Adam, Olmos, David, and Gahete, Manuel D.

Subjects
*PROSTATE cancer, *BREAST cancer, *CELL proliferation, *CANCER cells, *MESSENGER RNA
Abstract

Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease. Comprehensive analyses of SRSF6 alterations (copy number/mRNA/protein) were conducted across eight well-characterized PCa cohorts and the Hi-MYC transgenic model. SRSF6 was up-regulated in PCa samples, correlating with adverse clinical parameters. Functional assays, both in vitro (cell proliferation, migration, colony, and tumorsphere formation) and in vivo (xenograft tumors), demonstrated the impact of SRSF6 modulation on critical cancer hallmarks. Mechanistically, SRSF6 regulates the splicing pattern of the histone-chaperone HIRA, consequently affecting the activity of H3.3 in PCa and breast cancer cell models and disrupting pivotal oncogenic pathways (AR and E2F) in PCa cells. These findings underscore SRSF6 as a promising therapeutic target for PCa/advanced-stage PCa. [ABSTRACT FROM AUTHOR]

Published
2024
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32. BCL2 expression is enriched in advanced prostate cancer with features of lineage plasticity.

Author

Westaby, Daniel, Jiménez-Vacas, Juan M., Figueiredo, Ines, Rekowski, Jan, Pettinger, Claire, Gurel, Bora, Lundberg, Arian, Bogdan, Denisa, Buroni, Lorenzo, Neeb, Antje, Padilha, Ana, Taylor, Joe, Wanting Zeng, Das, Souvik, Hobern, Emily, Riisnaes, Ruth, Crespo, Mateus, Miranda, Susana, Ferreira, Ana, and Hanratty, Brian P.

Subjects
*PROSTATE cancer, *ANDROGEN receptors, *TRANSCRIPTION factors, *CASTRATION-resistant prostate cancer, *NEUROENDOCRINE cells, *EPITHELIAL-mesenchymal transition, *DNA methylation
Abstract

The widespread use of potent androgen receptor signaling inhibitors (ARSIs) has led to an increasing emergence of ARindependent castration-resistant prostate cancer (CRPC), typically driven by loss of AR expression, lineage plasticity, and transformation to prostate cancers (PCs) that exhibit phenotypes of neuroendocrine or basal-like cells. The anti-apoptotic protein BCL2 is upregulated in neuroendocrine cancers and may be a therapeutic target for this aggressive PC disease subset. There is an unmet clinical need, therefore, to clinically characterize BCL2 expression in metastatic CRPC (mCRPC), determine its association with AR expression, uncover its mechanisms of regulation, and evaluate BCL2 as a therapeutic target and/ or biomarker with clinical utility. Here, using multiple PC biopsy cohorts and models, we demonstrate that BCL2 expression is enriched in AR-negative mCRPC, associating with shorter overall survival and resistance to ARSIs. Moreover, high BCL2 expression associates with lineage plasticity features and neuroendocrine marker positivity. We provide evidence that BCL2 expression is regulated by DNA methylation, associated with epithelial-mesenchymal transition, and increased by the neuronal transcription factor ASCL1. Finally, BCL2 inhibition had antitumor activity in some, but not all, BCL2-positive PC models, highlighting the need for combination strategies to enhance tumor cell apoptosis and enrich response. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Thio-2 inhibits key signaling pathways required for the development and progression of castration resistant prostate cancer.

Author

Neeb, Antje, primary, Figueiredo, Ines, additional, Bogdan, Denisa, additional, Cato, Laura, additional, Stober, Jutta, additional, Jiménez-Vacas, Juan M., additional, Gourain, Victor, additional, Lee, Irene I., additional, Seeger, Rebecca, additional, Muhle-Goll, Claudia, additional, Gurel, Bora, additional, Welti, Jonathan, additional, Nava Rodrigues, Daniel, additional, Rekowski, Jan, additional, Qiu, Xintao, additional, Jiang, Yija, additional, Di Micco, Patrizio, additional, Mateos, Borja, additional, Bielskutė, Stasė, additional, Riisnaes, Ruth, additional, Ferreira, Ana, additional, Miranda, Susana, additional, Crespo, Mateus, additional, Buroni, Lorenzo, additional, Ning, Jian, additional, Carreira, Suzanne, additional, Bräse, Stefan, additional, Jung, Nicole, additional, Gräßle, Simone, additional, Swain, Amanda, additional, Salvatella, Xavier, additional, Plymate, Stephen R., additional, Al-Lazikani, Bissan, additional, Long, Henry W., additional, Yuan, Wei, additional, Brown, Myles, additional, Cato, Andrew C.B., additional, de Bono, Johann S., additional, and Sharp, Adam, additional

Published
2024
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34. Dysregulation of the splicing machinery is directly associated to aggressiveness of prostate cancer

Author

Jiménez-Vacas, Juan M., Herrero-Aguayo, Vicente, Montero-Hidalgo, Antonio J., Gómez-Gómez, Enrique, Fuentes-Fayos, Antonio C., León-González, Antonio J., Sáez-Martínez, Prudencio, Alors-Pérez, Emilia, Pedraza-Arévalo, Sergio, González-Serrano, Teresa, Reyes, Oscar, Martínez-López, Ana, Sánchez-Sánchez, Rafael, Ventura, Sebastián, Yubero-Serrano, Elena M., Requena-Tapia, María J., Castaño, Justo P., Gahete, Manuel D., and Luque, Raúl M.

Published
2020
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35. Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug

Author

Alors-Perez, Emilia, Blázquez-Encinas, Ricardo, Alcalá, Sonia, Viyuela-García, Cristina, Pedraza-Arevalo, Sergio, Herrero-Aguayo, Vicente, Jiménez-Vacas, Juan M., Mafficini, Andrea, Sánchez-Frías, Marina E., Cano, María T., Abollo-Jiménez, Fernando, Marín-Sanz, Juan A., Cabezas-Sainz, Pablo, Lawlor, Rita T., Luchini, Claudio, Sánchez, Laura, Sánchez-Hidalgo, Juan M., Ventura, Sebastián, Martin-Hijano, Laura, Gahete, Manuel D., Scarpa, Aldo, Arjona-Sánchez, Álvaro, Ibáñez-Costa, Alejandro, Sainz, Jr, Bruno, Luque, Raúl M., and Castaño, Justo P.

Published
2021
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36. Spliceosome component SF3B1 as novel prognostic biomarker and therapeutic target for prostate cancer

Author

Jiménez-Vacas, Juan M., Herrero-Aguayo, Vicente, Gómez-Gómez, Enrique, León-González, Antonio J., Sáez-Martínez, Prudencio, Alors-Pérez, Emilia, Fuentes-Fayos, Antonio C., Martínez-López, Ana, Sánchez-Sánchez, Rafael, González-Serrano, Teresa, López-Ruiz, Daniel J., Requena-Tapia, María J., Castaño, Justo P., Gahete, Manuel D., and Luque, Raúl M.

Published
2019
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37. Supplementary Figure from JMJD6 Is a Druggable Oxygenase That Regulates AR-V7 Expression in Prostate Cancer

Author

Paschalis, Alec, primary, Welti, Jonathan, primary, Neeb, Antje J., primary, Yuan, Wei, primary, Figueiredo, Ines, primary, Pereira, Rita, primary, Ferreira, Ana, primary, Riisnaes, Ruth, primary, Rodrigues, Daniel Nava, primary, Jiménez-Vacas, Juan M., primary, Kim, Soojin, primary, Uo, Takuma, primary, Micco, Patrizio Di, primary, Tumber, Anthony, primary, Islam, Md. Saiful, primary, Moesser, Marc A., primary, Abboud, Martine, primary, Kawamura, Akane, primary, Gurel, Bora, primary, Christova, Rossitza, primary, Gil, Veronica S., primary, Buroni, Lorenzo, primary, Crespo, Mateus, primary, Miranda, Susana, primary, Lambros, Maryou B., primary, Carreira, Suzanne, primary, Tunariu, Nina, primary, Alimonti, Andrea, primary, Al-Lazikani, Bissan, primary, Schofield, Christopher J., primary, Plymate, Stephen R., primary, Sharp, Adam, primary, and de Bono, Johann S., primary

Published
2023
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38. Data from JMJD6 Is a Druggable Oxygenase That Regulates AR-V7 Expression in Prostate Cancer

Author

Paschalis, Alec, primary, Welti, Jonathan, primary, Neeb, Antje J., primary, Yuan, Wei, primary, Figueiredo, Ines, primary, Pereira, Rita, primary, Ferreira, Ana, primary, Riisnaes, Ruth, primary, Rodrigues, Daniel Nava, primary, Jiménez-Vacas, Juan M., primary, Kim, Soojin, primary, Uo, Takuma, primary, Micco, Patrizio Di, primary, Tumber, Anthony, primary, Islam, Md. Saiful, primary, Moesser, Marc A., primary, Abboud, Martine, primary, Kawamura, Akane, primary, Gurel, Bora, primary, Christova, Rossitza, primary, Gil, Veronica S., primary, Buroni, Lorenzo, primary, Crespo, Mateus, primary, Miranda, Susana, primary, Lambros, Maryou B., primary, Carreira, Suzanne, primary, Tunariu, Nina, primary, Alimonti, Andrea, primary, Al-Lazikani, Bissan, primary, Schofield, Christopher J., primary, Plymate, Stephen R., primary, Sharp, Adam, primary, and de Bono, Johann S., primary

Published
2023
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39. Supplementary Table from JMJD6 Is a Druggable Oxygenase That Regulates AR-V7 Expression in Prostate Cancer

Author

Paschalis, Alec, primary, Welti, Jonathan, primary, Neeb, Antje J., primary, Yuan, Wei, primary, Figueiredo, Ines, primary, Pereira, Rita, primary, Ferreira, Ana, primary, Riisnaes, Ruth, primary, Rodrigues, Daniel Nava, primary, Jiménez-Vacas, Juan M., primary, Kim, Soojin, primary, Uo, Takuma, primary, Micco, Patrizio Di, primary, Tumber, Anthony, primary, Islam, Md. Saiful, primary, Moesser, Marc A., primary, Abboud, Martine, primary, Kawamura, Akane, primary, Gurel, Bora, primary, Christova, Rossitza, primary, Gil, Veronica S., primary, Buroni, Lorenzo, primary, Crespo, Mateus, primary, Miranda, Susana, primary, Lambros, Maryou B., primary, Carreira, Suzanne, primary, Tunariu, Nina, primary, Alimonti, Andrea, primary, Al-Lazikani, Bissan, primary, Schofield, Christopher J., primary, Plymate, Stephen R., primary, Sharp, Adam, primary, and de Bono, Johann S., primary

Published
2023
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40. Somatostatin, Cortistatin and Their Receptors Exert Antitumor Actions in Androgen-Independent Prostate Cancer Cells: Critical Role of Endogenous Cortistatin

Author

Sáez-Martínez, Prudencio, primary, Porcel-Pastrana, Francisco, additional, Pérez-Gómez, Jesús M., additional, Pedraza-Arévalo, Sergio, additional, Gómez-Gómez, Enrique, additional, Jiménez-Vacas, Juan M., additional, Gahete, Manuel D., additional, and Luque, Raúl M., additional

Published
2022
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43. Spliceosomic dysregulation unveilsNOVA1as an actionable therapeutic target in pancreatic neuroendocrine tumors

Author

Pedraza-Arevalo, Sergio, primary, Alors-Pérez, Emilia, additional, Blázquez-Encinas, Ricardo, additional, Herrera-Martínez, Aura D., additional, Jiménez-Vacas, Juan M., additional, Fuentes-Fayos, Antonio C., additional, Reyes, Óscar, additional, Ventura, Sebastián, additional, Sánchez-Sánchez, Rafael, additional, Ortega-Salas, Rosa, additional, Serrano-Blanch, Raquel, additional, Gálvez-Moreno, María A., additional, Gahete, Manuel D., additional, Ibáñez-Costa, Alejandro, additional, Luque, Raúl M., additional, and Castaño, Justo P., additional

Published
2022
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44. Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells

Author

León-González, Antonio J., primary, Sáez-Martínez, Prudencio, additional, Jiménez-Vacas, Juan M., additional, Herrero-Aguayo, Vicente, additional, Montero-Hidalgo, Antonio J., additional, Gómez-Gómez, Enrique, additional, Madrona, Andrés, additional, Castaño, Justo P., additional, Espartero, José L., additional, Gahete, Manuel D., additional, and Luque, Raúl M., additional

Published
2021
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46. In1-Ghrelin Splicing Variant as a Key Element in the Pathophysiological Association Between Obesity and Prostate Cancer

Author

Jiménez-Vacas, Juan M, primary, Montero-Hidalgo, Antonio J, additional, Gómez-Gómez, Enrique, additional, Fuentes-Fayos, Antonio C, additional, Ruiz-Pino, Francisco, additional, Guler, Ipek, additional, Camargo, Antonio, additional, Anglada, Francisco J, additional, Carrasco-Valiente, Julia, additional, Tena-Sempere, Manuel, additional, Sarmento-Cabral, André, additional, Castaño, Justo P, additional, Gahete, Manuel D, additional, and Luque, Raúl M, additional

Published
2021
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47. Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug

Author

Alors-Perez, Emilia, primary, Blázquez-Encinas, Ricardo, additional, Alcalá, Sonia, additional, Viyuela-García, Cristina, additional, Pedraza-Arevalo, Sergio, additional, Herrero-Aguayo, Vicente, additional, Jiménez-Vacas, Juan M, additional, Mafficini, Andrea, additional, Sánchez-Frías, Marina E, additional, Cano, María T, additional, Abollo-Jiménez, Fernando, additional, Marín-Sanz, Juan A, additional, Cabezas-Sainz, Pablo, additional, Lawlor, Rita T, additional, Luchini, Claudio, additional, Sánchez, Laura, additional, Sánchez-Hidalgo, Juan M, additional, Ventura, Sebastián, additional, Martin-Hijano, Laura, additional, Gahete, Manuel D, additional, Scarpa, Aldo, additional, Arjona-Sanchez, Alvaro, additional, Ibáñez-Costa, Alejandro, additional, Sainz, Bruno, additional, Luque, Raul M, additional, and Castano, Justo P, additional

Published
2021
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48. Potential therapeutic role of somatostatin and cortistatin in prostate cancer

Author

Gomez, Jesus Perez, primary, Sáez-Mart, Prudencio, additional, Jiménez-Vacas, Juan M., additional, Herrero-Aguayo, nez-Vacas, additional, Pedraza-Arévalo, Sergio, additional, Enrique, Gómez-Gómez, additional, León-González, Antonio J., additional, Martínez-Fuentes, Antonio J., additional, Castaño, Antonio J., additional, Gahete, Manuel D., additional, and Luque, Raúl M., additional

Published
2021
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50. Comparative cytotoxic activity of hydroxytyrosol and its semisynthetic lipophilic derivatives in prostate cancer cells

Author

Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Universidad de Sevilla. Departamento de Farmacología, León González, Antonio José, Sáez Martínez, Prudencio, Jiménez Vacas, Juan M., Herrero Aguayo, Vicente, Montero Hidalgo, Antonio J., Gómez Gómez, Enrique, Madrona, Andrés, Castaño, Justo P., Espartero Sánchez, José Luis, Gahete, Manuel D., Luque, Raúl M., Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Universidad de Sevilla. Departamento de Farmacología, León González, Antonio José, Sáez Martínez, Prudencio, Jiménez Vacas, Juan M., Herrero Aguayo, Vicente, Montero Hidalgo, Antonio J., Gómez Gómez, Enrique, Madrona, Andrés, Castaño, Justo P., Espartero Sánchez, José Luis, Gahete, Manuel D., and Luque, Raúl M.

Abstract

A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Be-cause of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

Published
2021

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