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Tumor Biology

MON-324 - Condensate-Driven Androgen Receptor Signaling Sustains Proliferation in Castration-Resistant Prostate Cancer

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Biomolecular condensates are dynamic, membraneless assemblies that coordinate essential cellular functions, including transcriptional regulation. Aberrant condensate behaviour is linked to diseases such as neurodegeneration and cancer. We previously established that androgen stimulation induces full-length androgen receptor (AR-FL) to assemble into nuclear condensates that support transcription in androgen-dependent prostate cancer. In advanced disease, known as castration-resistant prostate cancer (CRPC), therapeutic resistance frequently emerges through restoration of AR activity, notably via constitutively active splice variants such as AR-V7. However, the molecular basis of AR-V7-driven resistance remains poorly defined.
Here, we show that AR-V7 forms nuclear condensates autonomously, independent of androgen and AR-FL, in CRPC models. By comparing transcriptomes using RNA-sequencing of a condensate-impaired AR-V7 mutant that retains nuclear localization and DNA-binding capacity with wild-type AR-V7, we identify a condensate-dependent transcriptional program enriched for regulatory regions with high densities of androgen response elements. Strikingly, expression of these targets increases exponentially with AR-V7 abundance, whereas condensate-independent genes exhibit a linear response. AR-V7 condensates preferentially engage oncogenic pathways linked to proliferation, migration, and cell cycle control, including components of KRAS signaling. Functional disruption of condensate-dependent targets suppresses CRPC cell growth and motility. Consistent with these observations, this condensate-dependent transcriptional signature is elevated in CRPC patient samples and associates with aggressive and metastatic disease.
Collectively, our findings demonstrate that AR-V7 condensates drive a unique transcriptional state that supports androgen-independent tumor growth, providing a mechanistic explanation for treatment resistance and identifying condensate-dependent transcription as a potential therapeutic target in advanced prostate cancer.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*