SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer

In this study, we examined the chromatin landscape of AR-positive prostate cancer cells post-exposure to the AR inhibitor enzalutamide. We identified a novel regulator of cell plasticity, the homeobox transcription factor SIX2, whose motif is enriched in accessible chromatin regions after treatment. Depletion of SIX2 in androgen-independent PC-3 prostate cancer cells induced a switch from a stem-like to an epithelial state, resulting in reduced cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects were mediated through the downregulation of the Wnt/β-catenin signalling pathway and subsequent reduction of nuclear β-catenin. Collectively, our findings provide compelling evidence that the depletion of SIX2 may represent a promising strategy for overcoming the cell plasticity mechanisms driving antiandrogen resistance in prostate cancer.PMID:38554106 | DOI:10.1093/nar/gkae206

Source: Cell Research - March 30, 2024 Category: Cytology Authors: Noora Lepp änen Heidi Kaljunen Eerika Takala Roosa Kaarij ärvi Petri I M äkinen Seppo Yl ä-Herttuala Ilkka Paatero Ville Paakinaho Kirsi Ketola Source Type: research