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

ABSTRACT: The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting resistance to AR-targeted therapies. By examining the chromatin landscape of AR positive prostate cancer cells following exposure to the AR inhibitor enzalutamide, we have identified a novel regulator of cell plasticity, homeobox transcription factor SIX2, whose motif is enriched in accessible regions post-treatment. Our investigation demonstrates that depletion of SIX2 in androgen-independent PC-3 prostate cancer cells is sufficient to induce a switch from a stem-like to an epithelial state, leading to the reduction of key cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects are mediated through downregulation of Wnt/β-catenin signalling pathway and subsequent reduced nuclear localization of β-catenin. Collectively, our findings provide compelling evidence that depletion of SIX2 may represent a promising strategy for overcoming cell plasticity mechanisms driving AR resistance in prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235956 | GEO | 2024/03/19

REPOSITORIES: GEO

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