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11 results on '"Frederiks, Cynthia L"'

3. Chemotherapy-induced intestinal epithelial damage directly promotes galectin-9-driven modulation of T cell behavior

Author

MS Algemene Pediatrie Onderzoek 2, Cluster B, CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Cardiologie, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Onderzoek, Regenerative Medicine and Stem Cells, CMM Groep Coffer, CMM Sectie Stem Cells, SCT patientenzorg, Jansen, Suze A., Cutilli, Alessandro, de Koning, Coco, van Hoesel, Marliek, Frederiks, Cynthia L., Saiz Sierra, Leire, Nierkens, Stefan, Mokry, Michal, Nieuwenhuis, Edward E.S., Hanash, Alan M., Mocholi, Enric, Coffer, Paul J., Lindemans, Caroline A., MS Algemene Pediatrie Onderzoek 2, Cluster B, CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Cardiologie, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Onderzoek, Regenerative Medicine and Stem Cells, CMM Groep Coffer, CMM Sectie Stem Cells, SCT patientenzorg, Jansen, Suze A., Cutilli, Alessandro, de Koning, Coco, van Hoesel, Marliek, Frederiks, Cynthia L., Saiz Sierra, Leire, Nierkens, Stefan, Mokry, Michal, Nieuwenhuis, Edward E.S., Hanash, Alan M., Mocholi, Enric, Coffer, Paul J., and Lindemans, Caroline A.

Published
2024

5. Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation

Author

Roukens, M Guy, Frederiks, Cynthia L, Seinstra, Danielle, Braccioli, Luca, Khalil, Antoine A, Pals, Cornelieke, De Neck, Simon, Bornes, Laura, Beerling, Evelyne, Mokry, Michal, de Bruin, Alain, Westendorp, Bart, van Rheenen, Jacco, Coffer, Paul J, Pathobiologie DMPC, dPB CR, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Pathobiologie DMPC, dPB CR, Dep Biomolecular Health Sciences, Pathobiologie, and dPB RMSC

Subjects
Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Cellular differentiation, Breast Neoplasms, Cell Cycle Proteins, Biology, Article, SOXC Transcription Factors, Mice, SOX4, Breast cancer, Differentiation therapy, Genetics, medicine, Animals, Humans, Gene Silencing, Molecular Biology, Transcription factor, Mammary tumor, Cancer stem cells, Cancer, medicine.disease, Primary tumor, Gene Expression Regulation, Neoplastic, Organoids, Cancer research, Female, CRISPR-Cas Systems, Stem cell, Neoplasm Transplantation
Abstract

In breast cancer the transcription factor SOX4 has been shown to be associated with poor survival, increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a context-dependent manner that is determined by the cellular and epigenetic state. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model of breast cancer. Using CRISPR/Cas9 to abrogate SOX4 expression, we found that SOX4 is required for inhibiting differentiation by regulating a subset of genes that are highly activated in fetal mammary stem cells (fMaSC). In this way, SOX4 re-activates an oncogenic transcriptional program that is regulated in many progenitor cell-types during embryonic development. SOX4-knockout organoids are characterized by the presence of more differentiated cells that exhibit luminal or basal gene expression patterns, but lower expression of cell cycle genes. In agreement, primary tumor growth and metastatic outgrowth in the lungs are impaired in SOX4KO tumors. Finally, SOX4KO tumors show a severe loss in competitive capacity to grow out compared to SOX4-proficient cells in primary tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated and proliferative state. Therapeutic manipulation of SOX4 function could provide a novel strategy for cancer differentiation therapy, which would promote differentiation and inhibit cycling of tumor cells.

Published
2021
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6. Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation

Author

Pathobiologie DMPC, dPB CR, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Roukens, M Guy, Frederiks, Cynthia L, Seinstra, Danielle, Braccioli, Luca, Khalil, Antoine A, Pals, Cornelieke, De Neck, Simon, Bornes, Laura, Beerling, Evelyne, Mokry, Michal, de Bruin, Alain, Westendorp, Bart, van Rheenen, Jacco, Coffer, Paul J, Pathobiologie DMPC, dPB CR, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Roukens, M Guy, Frederiks, Cynthia L, Seinstra, Danielle, Braccioli, Luca, Khalil, Antoine A, Pals, Cornelieke, De Neck, Simon, Bornes, Laura, Beerling, Evelyne, Mokry, Michal, de Bruin, Alain, Westendorp, Bart, van Rheenen, Jacco, and Coffer, Paul J

Published
2021

7. Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation

Author

CMM Groep Coffer, Infection & Immunity, Cancer, CMM Groep de Rooij, Onderzoek Medische Oncologie, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Roukens, M Guy, Frederiks, Cynthia L, Seinstra, Danielle, Braccioli, Luca, Khalil, Antoine A, Pals, Cornelieke, De Neck, Simon, Bornes, Laura, Beerling, Evelyne, Mokry, Michal, de Bruin, Alain, Westendorp, Bart, van Rheenen, Jacco, Coffer, Paul J, CMM Groep Coffer, Infection & Immunity, Cancer, CMM Groep de Rooij, Onderzoek Medische Oncologie, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Roukens, M Guy, Frederiks, Cynthia L, Seinstra, Danielle, Braccioli, Luca, Khalil, Antoine A, Pals, Cornelieke, De Neck, Simon, Bornes, Laura, Beerling, Evelyne, Mokry, Michal, de Bruin, Alain, Westendorp, Bart, van Rheenen, Jacco, and Coffer, Paul J

Published
2021

8. C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition

Author

CMM, CMM Groep Coffer, Infection & Immunity, Cancer, CMM Sectie Celbiologie, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Lourenço, Ana Rita, Roukens, M. Guy, Seinstra, Danielle, Frederiks, Cynthia L., Pals, Cornelieke E., Vervoort, Stephin J., Margarido, Andreia S., van Rheenen, Jacco, Coffer, Paul J., CMM, CMM Groep Coffer, Infection & Immunity, Cancer, CMM Sectie Celbiologie, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Lourenço, Ana Rita, Roukens, M. Guy, Seinstra, Danielle, Frederiks, Cynthia L., Pals, Cornelieke E., Vervoort, Stephin J., Margarido, Andreia S., van Rheenen, Jacco, and Coffer, Paul J.

Published
2020

9. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis

Author

Vervoort, Stephin J, De Jong, Olivier G, Roukens, M Guy, Frederiks, Cynthia L, Vermeulen, Jeroen F, Lourenço, Ana Rita, Bella, Laura, Vidakovic, Ana Tufegdzic, Sandoval, José L, Moelans, Cathy, Van Amersfoort, Miranda, Dallman, Margaret J, Bruna, Alejandra, Caldas, Carlos, Nieuwenhuis, Edward, Van Der Wall, Elsken, Derksen, Patrick, Van Diest, Paul, Verhaar, Marianne C, Lam, Eric W-F, Mokry, Michal, Coffer, Paul J, Bruna, Alejandra [0000-0003-1214-9665], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository

Subjects
Transcription, Genetic, QH301-705.5, Science, Breast Neoplasms, Epigenesis, Genetic, SOXC Transcription Factors, breast cancer, cell biology, Animals, Humans, Gene Regulatory Networks, RNA, Messenger, human, Biology (General), Neoplasm Metastasis, Promoter Regions, Genetic, mouse, cancer biology, tumor biology, Neovascularization, Pathologic, Endothelin-1, Gene Expression Profiling, Epithelial Cells, zebrafish, Survival Analysis, Xenograft Model Antitumor Assays, Chromatin, Gene Expression Regulation, Neoplastic, HEK293 Cells, Culture Media, Conditioned, Trans-Activators, Medicine, Female, EDN1, SOX4, Angiogenesis, Research Article
Abstract

The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in patients with breast cancer. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role for this transcription factor in promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways.

Published
2018

10. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis

Author

CMM Groep Coffer, CDL Nanomedicine, Cancer, Infection & Immunity, Pathologie Algemene Pat.zorg, Unit Opleiding Aios, Pathologie Groep Van Diest, Pathologie, Divisie Kinderen, Child Health, Regenerative Medicine and Stem Cells, Zorg en O&O, Cancer Center Patiëntenzorg, Speerpunt Cancer, Pathologie Groep Derksen, Nefro Vasculaire Geneeskunde, Circulatory Health, MDL onderzoek 1, Onderzoek, Vervoort, Stephin J., de Jong, Olivier G., Guy Roukens, M., Frederiks, Cynthia L., Vermeulen, Jeroen F., Lourenço, Ana Rita, Bella, Laura, Vidakovic, Ana Tufegdzic, Sandoval, José L., Moelans, Cathy, van Amersfoort, Miranda, Dallman, Margaret J., Bruna, Alejandra, Caldas, Carlos, Nieuwenhuis, Edward, van der Wall, Elsken, Derksen, Patrick, van Diest, Paul, Verhaar, Marianne C., Lam, Eric W.F., Mokry, Michal, Coffer, Paul J., CMM Groep Coffer, CDL Nanomedicine, Cancer, Infection & Immunity, Pathologie Algemene Pat.zorg, Unit Opleiding Aios, Pathologie Groep Van Diest, Pathologie, Divisie Kinderen, Child Health, Regenerative Medicine and Stem Cells, Zorg en O&O, Cancer Center Patiëntenzorg, Speerpunt Cancer, Pathologie Groep Derksen, Nefro Vasculaire Geneeskunde, Circulatory Health, MDL onderzoek 1, Onderzoek, Vervoort, Stephin J., de Jong, Olivier G., Guy Roukens, M., Frederiks, Cynthia L., Vermeulen, Jeroen F., Lourenço, Ana Rita, Bella, Laura, Vidakovic, Ana Tufegdzic, Sandoval, José L., Moelans, Cathy, van Amersfoort, Miranda, Dallman, Margaret J., Bruna, Alejandra, Caldas, Carlos, Nieuwenhuis, Edward, van der Wall, Elsken, Derksen, Patrick, van Diest, Paul, Verhaar, Marianne C., Lam, Eric W.F., Mokry, Michal, and Coffer, Paul J.

Published
2018

11. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis.

Author

Vervoort SJ, de Jong OG, Roukens MG, Frederiks CL, Vermeulen JF, Lourenço AR, Bella L, Vidakovic AT, Sandoval JL, Moelans C, van Amersfoort M, Dallman MJ, Bruna A, Caldas C, Nieuwenhuis E, van der Wall E, Derksen P, van Diest P, Verhaar MC, Lam EW, Mokry M, and Coffer PJ

Subjects
Animals, Breast Neoplasms pathology, Chromatin metabolism, Culture Media, Conditioned pharmacology, Endothelin-1 metabolism, Epigenesis, Genetic, Epithelial Cells drug effects, Epithelial Cells metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Gene Regulatory Networks, HEK293 Cells, Humans, Neoplasm Metastasis, Promoter Regions, Genetic genetics, RNA, Messenger genetics, RNA, Messenger metabolism, SOXC Transcription Factors genetics, Survival Analysis, Trans-Activators metabolism, Xenograft Model Antitumor Assays, Zebrafish, Breast Neoplasms blood supply, Breast Neoplasms genetics, Neovascularization, Pathologic genetics, SOXC Transcription Factors metabolism, Transcription, Genetic
Abstract

The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in patients with breast cancer. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role for this transcription factor in promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways., Competing Interests: SV, Od, MR, CF, JV, AL, LB, AV, JS, CM, Mv, MD, AB, CC, EN, Ev, PD, Pv, MV, EL, MM, PC No competing interests declared, (© 2018, Vervoort et al.)

Published
2018
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