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Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer

ABSTRACT: Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer

PROVIDER: PRJNA1108768 | ENA |

REPOSITORIES: ENA

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Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (scRNA-Seq)

Project description:Resistance to therapy is a major challenge in castration-resistant prostate cancer (CRPC). Lineage plasticity towards a neuroendocrine phenotype enables CRPC to adapt and survive targeted-therapies. However, the molecular mechanisms of epigenetic reprogramming during this process are still poorly understood. Here we show that the protein kinase PKCl/i phosphorylates the epigenetic regulator enhancer of zeste homologue 2 (EZH2) to regulate its proteasomal degradation and maintain EZH2 as part of the canonical polycomb repressive complex (PRC2). Loss of PKCl/i promotes a switch during enzalutamide treatment to a non-canonical EZH2 cistrome that triggers the transcriptional activation of the translational machinery to induce a transforming growth factor b (TGFb) resistance program. The increased reliance on protein synthesis creates a synthetic vulnerability in PKCl/i-deficient CRPC.

2024-10-22 | GSE266955 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (CUT&RUN)

2024-10-22 | GSE266949 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (CUT&RUN) II

2024-10-22 | GSE272471 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq polysome)

2024-10-22 | GSE266954 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq organoids)

2024-10-22 | GSE266951 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq LNCaP)

2024-10-22 | GSE266950 | GEO

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (CUT&RUN)

Project description:Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (CUT&RUN)

| PRJNA1108766 | ENA

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (scRNA-Seq)

Project description:Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (scRNA-Seq)

| PRJNA1108777 | ENA

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq LNCaP)

Project description:Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq LNCaP)

| PRJNA1108767 | ENA

Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq organoids)

Project description:Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq organoids)

| PRJNA1108773 | ENA

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