Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy.
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| Format: | Artículo científico |
| Language: | en |
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EMBO molecular medicine
2026
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| author | Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent |
| author_facet | Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent |
| collection | PubMed - marine biology |
| contents | Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy. Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent Male Animals Mice Humans Prostatic Neoplasms Fos-Related Antigen 1 Prostatic Neoplasms, Castration-Resistant Mice, Knockout PTEN Phosphohydrolase Androgen Antagonists Transcription Factor AP-1 Cell Line, Tumor Proto-Oncogene Proteins c-fos A critical knowledge gap in prostate cancer research is understanding whether castration-tolerant progenitor-like cells that reside in treatment-naïve tumors play a direct role in therapy resistance and tumor progression. Herein, we reveal that the castration tolerance of LSC (Lin, Sca-1, CD49f) progenitor cells, the mouse equivalent of human prostatic Club cells, arises not from intrinsic properties, but from significant transcriptional reprogramming. Utilizing single-cell RNA sequencing of LSC cells isolated from prostate-specific Pten-deficient (Pten) mice, we identify the emergence of castration-resistant LSC cells enriched in stem-like features, driven by the transcription factor FOSL1/AP-1. We demonstrate that cells exhibiting Pten LSC characteristics are prevalent in aggressive double-negative prostate cancer (DNPC) subtypes recently identified in human castration-resistant prostate cancer (CRPC). Furthermore, our findings show that the dual-targeting agents JQ-1 and CX-6258-focused on FOSL1/AP-1 and PIM kinases, respectively-effectively suppress both the progenitor properties and the growth of mouse and human DNPC surrogates in vitro and in vivo. Thus, early eradication of castration-tolerant Club-like cells presents a promising therapeutic strategy to mitigate prostate cancer progression toward CRPC. |
| format | Artículo científico |
| id | pubmed_41629661 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | EMBO molecular medicine |
| record_format | pubmed |
| spellingShingle | Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy. Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent Male Animals Mice Humans Prostatic Neoplasms Fos-Related Antigen 1 Prostatic Neoplasms, Castration-Resistant Mice, Knockout PTEN Phosphohydrolase Androgen Antagonists Transcription Factor AP-1 Cell Line, Tumor Proto-Oncogene Proteins c-fos Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy. Baurès, Manon Vieira Aleixo, Anne-Sophie Pacreau, Emeline Koshy, Aysis Friedrich, Vanessa Diedisheim, Marc Raigel, Martin Hua, Yichao Dariane, Charles Boutillon, Florence Kenner, Lukas Marine, Jean-Christophe Laverny, Gilles Metzger, Daniel Rambow, Florian Guidotti, Jacques-Emmanuel Goffin, Vincent Male Animals Mice Humans Prostatic Neoplasms Fos-Related Antigen 1 Prostatic Neoplasms, Castration-Resistant Mice, Knockout PTEN Phosphohydrolase Androgen Antagonists Transcription Factor AP-1 Cell Line, Tumor Proto-Oncogene Proteins c-fos A critical knowledge gap in prostate cancer research is understanding whether castration-tolerant progenitor-like cells that reside in treatment-naïve tumors play a direct role in therapy resistance and tumor progression. Herein, we reveal that the castration tolerance of LSC (Lin, Sca-1, CD49f) progenitor cells, the mouse equivalent of human prostatic Club cells, arises not from intrinsic properties, but from significant transcriptional reprogramming. Utilizing single-cell RNA sequencing of LSC cells isolated from prostate-specific Pten-deficient (Pten) mice, we identify the emergence of castration-resistant LSC cells enriched in stem-like features, driven by the transcription factor FOSL1/AP-1. We demonstrate that cells exhibiting Pten LSC characteristics are prevalent in aggressive double-negative prostate cancer (DNPC) subtypes recently identified in human castration-resistant prostate cancer (CRPC). Furthermore, our findings show that the dual-targeting agents JQ-1 and CX-6258-focused on FOSL1/AP-1 and PIM kinases, respectively-effectively suppress both the progenitor properties and the growth of mouse and human DNPC surrogates in vitro and in vivo. Thus, early eradication of castration-tolerant Club-like cells presents a promising therapeutic strategy to mitigate prostate cancer progression toward CRPC. |
| title | Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy. |
| topic | Male Animals Mice Humans Prostatic Neoplasms Fos-Related Antigen 1 Prostatic Neoplasms, Castration-Resistant Mice, Knockout PTEN Phosphohydrolase Androgen Antagonists Transcription Factor AP-1 Cell Line, Tumor Proto-Oncogene Proteins c-fos |
| url | https://pubmed.ncbi.nlm.nih.gov/41629661/ |