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2. Glucocorticoid treatment influences prostate cancer cell growth and the tumor microenvironment via altered glucocorticoid receptor signaling in prostate fibroblasts

Author

Eigentler, Andrea, Handle, Florian, Schanung, Silvia, Degen, Antonia, Hackl, Hubert, Erb, Holger H. H., Fotakis, Georgios, Hoefer, Julia, Ploner, Christian, Jöhrer, Karin, Heidegger, Isabel, Pircher, Andreas, Klotz, Werner, Herold, Manfred, Schäfer, Georg, Culig, Zoran, and Puhr, Martin

Published
2024
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3. Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization

Author

Rauchenwald, Tina, Handle, Florian, Connolly, Catherine E., Degen, Antonia, Seifarth, Christof, Hermann, Martin, Tripp, Christoph H., Wilflingseder, Doris, Lobenwein, Susanne, Savic, Dragana, Pölzl, Leo, Morandi, Evi M., Wolfram, Dolores, Skvortsova, Ira-Ida, Stoitzner, Patrizia, Haybaeck, Johannes, Konschake, Marko, Pierer, Gerhard, and Ploner, Christian

Published
2023
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7. MED12 and CDK8/19 Modulate Androgen Receptor Activity and Enzalutamide Response in Prostate Cancer.

Author

Andolfi, Chiara, Bartolini, Caterina, Morales, Elisa, Gündoğdu, Büşra, Puhr, Martin, Guzman, Juan, Wach, Sven, Taubert, Helge, Aigner, Achim, Eder, Iris E, Handle, Florian, and Culig, Zoran

Subjects
CANCER cell proliferation, PROSTATE cancer patients, CANCER patients, GENE expression, PROSTATE-specific antigen, ANDROGEN receptors
Abstract

Prostate cancer progression is driven by androgen receptor (AR) activity, which is a target for therapeutic approaches. Enzalutamide is an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One of these mechanisms is the expression of AR-V7, a constitutively active AR splice variant. The Mediator complex is a multisubunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase (CDK)8, or its paralog CDK19, are components of the kinase module that regulates the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and the enzalutamide response. We inhibited MED12 expression and CDK8/19 activity in LNCaP (AR+, enzalutamide-sensitive), 22Rv1 (AR-V7+, enzalutamide-resistant), and PC3 (AR−, enzalutamide-insensitive) cells. Both MED12 and CDK8/19 inhibition reduced cell proliferation in all cell lines, and MED12 inhibition reduced proliferation in the respective 3D spheroids. MED12 knockdown significantly inhibited c-Myc protein expression and signaling pathways. In 22Rv1 cells, it consistently inhibited the AR response, prostate-specific antigen (PSA) secretion, AR target genes, and AR-V7 expression. Combined with enzalutamide, MED12 inhibition additively decreased the AR activity in both LNCaP and 22Rv1 cells. CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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9. The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation

Author

El Kharraz, Sarah, Dubois, Vanessa, van Royen, Martin E, Houtsmuller, Adriaan B, Pavlova, Ekatarina, Atanassova, Nina, Nguyen, Tien, Voet, Arnout, Eerlings, Roy, Handle, Florian, Prekovic, Stefan, Smeets, Elien, Moris, Lisa, Devlies, Wout, Ohlsson, Claes, Poutanen, Matti, Verstrepen, Kevin J, Carmeliet, Geert, Launonen, Kaisa-Mari, Helminen, Laura, Palvimo, Jorma J, Libert, Claude, Vanderschueren, Dirk, Helsen, Christine, and Claessens, Frank

Published
2021
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10. Glucocorticoid treatment influences prostate cancer cell growth and the tumor microenvironment via altered glucocorticoid receptor signaling in prostate fibroblasts

Author

Eigentler, Andrea, primary, Handle, Florian, additional, Schanung, Silvia, additional, Degen, Antonia, additional, Hackl, Hubert, additional, Erb, Holger H. H., additional, Fotakis, Georgios, additional, Hoefer, Julia, additional, Ploner, Christian, additional, Jöhrer, Karin, additional, Heidegger, Isabel, additional, Pircher, Andreas, additional, Klotz, Werner, additional, Herold, Manfred, additional, Schäfer, Georg, additional, Culig, Zoran, additional, and Puhr, Martin, additional

Published
2023
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11. Rational evolution for altering the ligand preference of estrogen receptor alpha.

Author

Eerlings, Roy, Gupta, Purvi, Lee, Xiao Yin, Nguyen, Tien, El Kharraz, Sarah, Handle, Florian, Smeets, Elien, Moris, Lisa, Devlies, Wout, Vandewinkel, Bram, Thiry, Irina, Ta, Duy Tien, Gorkovskiy, Anton, Voordeckers, Karin, Henckaerts, Els, Pinheiro, Vitor B., Claessens, Frank, Verstrepen, Kevin J., Voet, Arnout, and Helsen, Christine

Abstract

Estrogen receptor α is commonly used in synthetic biology to control the activity of genome editing tools. The activating ligands, estrogens, however, interfere with various cellular processes, thereby limiting the applicability of this receptor. Altering its ligand preference to chemicals of choice solves this hurdle but requires adaptation of unspecified ligand‐interacting residues. Here, we provide a solution by combining rational protein design with multi‐site‐directed mutagenesis and directed evolution of stably integrated variants in Saccharomyces cerevisiae. This method yielded an estrogen receptor variant, named TERRA, that lost its estrogen responsiveness and became activated by tamoxifen, an anti‐estrogenic drug used for breast cancer treatment. This tamoxifen preference of TERRA was maintained in mammalian cells and mice, even when fused to Cre recombinase, expanding the mammalian synthetic biology toolbox. Not only is our platform transferable to engineer ligand preference of any steroid receptor, it can also profile drug‐resistance landscapes for steroid receptor‐targeted therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Data from Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, primary, Gevaert, Thomas, primary, Davicioni, Elai, primary, Boeckx, Bram, primary, Lambrechts, Diether, primary, Helsen, Christine, primary, Handle, Florian, primary, Ghesquière, Bart, primary, Soenen, Stefaan, primary, Smeets, Elien, primary, Eerlings, Roy, primary, El Kharraz, Sarah, primary, Devlies, Wout, primary, Karnes, R. Jeffrey, primary, Lotan, Tamara, primary, Van Poppel, Hendrik, primary, Joniau, Steven, primary, and Claessens, Frank, primary

Published
2023
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18. Supplementary Data from Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, primary, Gevaert, Thomas, primary, Davicioni, Elai, primary, Boeckx, Bram, primary, Lambrechts, Diether, primary, Helsen, Christine, primary, Handle, Florian, primary, Ghesquière, Bart, primary, Soenen, Stefaan, primary, Smeets, Elien, primary, Eerlings, Roy, primary, El Kharraz, Sarah, primary, Devlies, Wout, primary, Karnes, R. Jeffrey, primary, Lotan, Tamara, primary, Van Poppel, Hendrik, primary, Joniau, Steven, primary, and Claessens, Frank, primary

Published
2023
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20. Supplementary Figure from Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, primary, Gevaert, Thomas, primary, Davicioni, Elai, primary, Boeckx, Bram, primary, Lambrechts, Diether, primary, Helsen, Christine, primary, Handle, Florian, primary, Ghesquière, Bart, primary, Soenen, Stefaan, primary, Smeets, Elien, primary, Eerlings, Roy, primary, El Kharraz, Sarah, primary, Devlies, Wout, primary, Karnes, R. Jeffrey, primary, Lotan, Tamara, primary, Van Poppel, Hendrik, primary, Joniau, Steven, primary, and Claessens, Frank, primary

Published
2023
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21. Supplementary Figure 1 from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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22. Supplementary Figure 2 from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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25. Supplementary Table from Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, primary, Gevaert, Thomas, primary, Davicioni, Elai, primary, Boeckx, Bram, primary, Lambrechts, Diether, primary, Helsen, Christine, primary, Handle, Florian, primary, Ghesquière, Bart, primary, Soenen, Stefaan, primary, Smeets, Elien, primary, Eerlings, Roy, primary, El Kharraz, Sarah, primary, Devlies, Wout, primary, Karnes, R. Jeffrey, primary, Lotan, Tamara, primary, Van Poppel, Hendrik, primary, Joniau, Steven, primary, and Claessens, Frank, primary

Published
2023
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27. Supplementary Figure 5 from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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30. Supplementary Figure 4 from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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31. Data from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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32. Supplementary Figure 3 from The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models

Author

Handle, Florian, primary, Puhr, Martin, primary, Schaefer, Georg, primary, Lorito, Nicla, primary, Hoefer, Julia, primary, Gruber, Martina, primary, Guggenberger, Fabian, primary, Santer, Frédéric R., primary, Marques, Rute B., primary, van Weerden, Wytske M., primary, Claessens, Frank, primary, Erb, Holger H.H., primary, and Culig, Zoran, primary

Published
2023
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33. Figure S1 from The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy

Author

Puhr, Martin, primary, Hoefer, Julia, primary, Eigentler, Andrea, primary, Ploner, Christian, primary, Handle, Florian, primary, Schaefer, Georg, primary, Kroon, Jan, primary, Leo, Angela, primary, Heidegger, Isabel, primary, Eder, Iris, primary, Culig, Zoran, primary, Van der Pluijm, Gabri, primary, and Klocker, Helmut, primary

Published
2023
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34. Table S1 from The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy

Author

Puhr, Martin, primary, Hoefer, Julia, primary, Eigentler, Andrea, primary, Ploner, Christian, primary, Handle, Florian, primary, Schaefer, Georg, primary, Kroon, Jan, primary, Leo, Angela, primary, Heidegger, Isabel, primary, Eder, Iris, primary, Culig, Zoran, primary, Van der Pluijm, Gabri, primary, and Klocker, Helmut, primary

Published
2023
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35. Suppl Figure legends from The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy

Author

Puhr, Martin, primary, Hoefer, Julia, primary, Eigentler, Andrea, primary, Ploner, Christian, primary, Handle, Florian, primary, Schaefer, Georg, primary, Kroon, Jan, primary, Leo, Angela, primary, Heidegger, Isabel, primary, Eder, Iris, primary, Culig, Zoran, primary, Van der Pluijm, Gabri, primary, and Klocker, Helmut, primary

Published
2023
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36. RF03 | PMON286 Engineering Steroid Receptors to Respond to Chemicals of Choice

Author

Claessens, Frank, primary, Eerlings, Roy, additional, Gupta, Purvi, additional, Lee, Xiao Yin, additional, Kharraz, Sarah E, additional, Jacquemyn, Maarten, additional, Vandewinkel, Bram, additional, Munter, Sofie D, additional, Nguyen, Tien, additional, Handle, Florian, additional, Smeets, Elien, additional, Moris, Lisa, additional, Devlies, Wout, additional, Voordeckers, Karin, additional, Gorkovskiy, Anton, additional, Henckaerts, Els, additional, Daelemans, Dirk, additional, Verstrepen, Kevin J, additional, Voet, Arnout, additional, and Helsen, Christine, additional

Published
2022
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43. Abstract 401: Single-cell transcriptome and chromatin sequencing uncover gene expression and gene regulatory patterns associated with enzalutamide resistance

Author

Taavitsainen, Sinja, primary, Engedal, Nikolai, additional, Cao, Shaolong, additional, Handle, Florian, additional, Erickson, Andrew, additional, Prekovic, Stefan, additional, Wetterskog, Daniel, additional, Tolonen, Teemu, additional, Vuorinen, Elisa M., additional, Kiviaho, Antti, additional, Nätkin, Reetta, additional, Häkkinen, Tomi, additional, Devlies, Wout, additional, Henttinen, Sallamari, additional, Kaarijärvi, Roosa, additional, Lahnalampi, Mari, additional, Kaljunen, Heidi, additional, Nowakowska, Karolina, additional, Syvälä, Heimo, additional, Bläuer, Merja, additional, Cremaschi, Paolo, additional, Claessens, Frank, additional, Visakorpi, Tapio, additional, Tammela, Teuvo L., additional, Murtola, Teemu, additional, Granberg, Kirsi J., additional, Lamb, Alastair D., additional, Ketola, Kirsi, additional, Mills, Ian G., additional, Attard, Gerhardt, additional, Wang, Wenyi, additional, Nykter, Matti, additional, and Urbanucci, Alfonso, additional

Published
2022
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44. A disease‐associated missense mutation in CYP4F3 affects the metabolism of leukotriene B4 via disruption of electron transfer

Author

Smeets, Elien, primary, Huang, Shengyun, additional, Lee, Xiao Yin, additional, Van Nieuwenhove, Erika, additional, Helsen, Christine, additional, Handle, Florian, additional, Moris, Lisa, additional, El Kharraz, Sarah, additional, Eerlings, Roy, additional, Devlies, Wout, additional, Willemsen, Mathijs, additional, Bücken, Leoni, additional, Prezzemolo, Teresa, additional, Humblet‐Baron, Stephanie, additional, Voet, Arnout, additional, Rochtus, Anne, additional, Van Schepdael, Ann, additional, de Zegher, Francis, additional, and Claessens, Frank, additional

Published
2022
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46. Antizyme Inhibitor 1 regulates matrikine expression and enhances the metastatic potential of aggressive primary prostate cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, additional, Gevaert, Thomas, additional, Davicioni, Elai, additional, Boeckx, Bram, additional, Lambrechts, Diether, additional, Helsen, Christine, additional, Handle, Florian, additional, Ghesquiere, Bart, additional, Soenen, Stefaan, additional, Smeets, Elien, additional, Eerlings, Roy, additional, El Kharraz, Sarah, additional, Devlies, Wout, additional, Karnes, R. Jeffrey, additional, Lotan, Tamara, additional, Van Poppel, Hendrik, additional, Joniau, Steven, additional, and Claessens, Frank, additional

Published
2022
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47. The stem cell inhibitor salinomycin decreases colony formation potential and tumor‐initiating population in docetaxel‐sensitive and docetaxel‐resistant prostate cancer cells

Author

Gruber, Martina, Handle, Florian, and Culig, Zoran

Subjects
prostate cancer stem cells, Male, CD24 Antigen, Prostatic Neoplasms, Original Articles, Docetaxel, urologic and male genital diseases, colony formation, automated analysis, inhibition of holoclones, Hyaluronan Receptors, Drug Resistance, Neoplasm, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, PC-3 Cells, Neoplastic Stem Cells, Humans, Original Article, colony types, Pyrans
Abstract

Background Prostate cancer (PCa) is one of the most frequently diagnosed tumors in men. In general, therapies for localized PCa are curative. However, treatment of advanced PCa is considered palliative since development of therapy resistance occurs rapidly. It has been shown that tumor‐initiating cells are likely involved in therapy resistance. They are not eliminated by conventional therapies and thereby lead to tumor progression and relapse. The aim of this study was to evaluate the effects of the known stem cell inhibitor salinomycin on this critical subpopulation of cells. Methods Expression of the cell surface markers CD24 and CD44 was assessed by immunofluorescence and fluorescence‐activated cell sorting. Colony formation efficiency and classification of colony types with varying tumor‐initiating potential (holoclones, meroclones, and paraclones) were analyzed in an automated way by the newly developed CATCH‐colonies software in the absence or presence of salinomycin. Results Automated high‐resolution colony formation analysis consistently identified the various colony types in a broad range of PCa cell lines. Serial clonogenic assays confirmed that holoclones show the highest colony formation potential and maintain their tumor‐initiating capacity over multiple rounds. Furthermore, holoclones showed high expression of CD44, while CD24 was not expressed in these clones, thus representing the well‐described tumor‐initiating CD24−/CD44high population. Salinomycin decreased the CD24−/CD44high population in both docetaxel‐sensitive PC3 and docetaxel‐resistant (DR) PC3‐DR. Moreover, treatment of PC3, DU145, PC3‐DR, and DU145‐DR with salinomycin led to a significant reduction in the colony formation potential by targeting the colonies with high tumor‐initiating potential. Conclusions Taken together, we demonstrated that salinomycin specifically targets the tumor‐initiating cell population in docetaxel‐sensitive and docetaxel‐resistant PCa cells and may represent a potential therapeutic approach for the treatment of advanced PCa.

Published
2019

49. The stem cell inhibitor salinomycin decreases colony formation potential and tumor-initiating population in docetaxel-sensitive and docetaxel-resistant prostate cancer cells

Author

Gruber, Martina, Handle, Florian, and Culig, Zoran

Subjects
prostate cancer stem cells, DRUG-RESISTANCE, Endocrinology & Metabolism, Science & Technology, Urology & Nephrology, urologic and male genital diseases, colony types, Life Sciences & Biomedicine, colony formation, automated analysis, inhibition of holoclones
Abstract

BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed tumors in men. In general, therapies for localized PCa are curative. However, treatment of advanced PCa is considered palliative since development of therapy resistance occurs rapidly. It has been shown that tumor-initiating cells are likely involved in therapy resistance. They are not eliminated by conventional therapies and thereby lead to tumor progression and relapse. The aim of this study was to evaluate the effects of the known stem cell inhibitor salinomycin on this critical subpopulation of cells. METHODS: Expression of the cell surface markers CD24 and CD44 was assessed by immunofluorescence and fluorescence-activated cell sorting. Colony formation efficiency and classification of colony types with varying tumor-initiating potential (holoclones, meroclones, and paraclones) were analyzed in an automated way by the newly developed CATCH-colonies software in the absence or presence of salinomycin. RESULTS: Automated high-resolution colony formation analysis consistently identified the various colony types in a broad range of PCa cell lines. Serial clonogenic assays confirmed that holoclones show the highest colony formation potential and maintain their tumor-initiating capacity over multiple rounds. Furthermore, holoclones showed high expression of CD44, while CD24 was not expressed in these clones, thus representing the well-described tumor-initiating CD24- /CD44high population. Salinomycin decreased the CD24- /CD44high population in both docetaxel-sensitive PC3 and docetaxel-resistant (DR) PC3-DR. Moreover, treatment of PC3, DU145, PC3-DR, and DU145-DR with salinomycin led to a significant reduction in the colony formation potential by targeting the colonies with high tumor-initiating potential. CONCLUSIONS: Taken together, we demonstrated that salinomycin specifically targets the tumor-initiating cell population in docetaxel-sensitive and docetaxel-resistant PCa cells and may represent a potential therapeutic approach for the treatment of advanced PCa. ispartof: PROSTATE vol:80 issue:3 pages:267-273 ispartof: location:United States status: published

Published
2020

50. Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Author

Taavitsainen, Sinja, primary, Engedal, Nikolai, additional, Cao, Shaolong, additional, Handle, Florian, additional, Erickson, Andrew, additional, Prekovic, Stefan, additional, Wetterskog, Daniel, additional, Tolonen, Teemu, additional, Vuorinen, Elisa, additional, Kiviaho, Antti, additional, Nätkin, Reetta, additional, Häkkinen, Tomi, additional, Devlies, Wout, additional, Henttinen, Sallamari, additional, Kaarijärvi, Roosa, additional, Lahnalampi, Mari, additional, Kaljunen, Heidi, additional, Nowakowska, Karolina, additional, Syvälä, Heimo, additional, Bläuer, Merja, additional, Cremaschi, Paolo, additional, Claessens, Frank, additional, Visakorpi, Tapio, additional, Tammela, Teuvo, additional, Murtola, Teemu, additional, Granberg, Kirsi, additional, Lamb, Alastair, additional, Ketola, Kirsi, additional, Mills, Ian, additional, Attard, Gerhardt, additional, Wang, Wenyi, additional, Nykter, Matti, additional, and Urbanucci, Alfonso, additional

Published
2021
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