PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer.

ABSTRACT:

Background

Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled.

Methods

By unbiased cross-correlation between RNA-sequencing, database signatures, and ChIP analysis, combining in vitro cell lines and in vivo animal models, we identified that PCK1 is a pivotal regulator in therapy-induced neuroendocrine differentiation of prostate cancer through a LIF/ZBTB46-driven glucose metabolism pathway.

Results

Upregulation of PCK1 supports cell proliferation and reciprocally increases ZBTB46 levels

SUBMITTER: Wen YC 

PROVIDER: S-EPMC8888753 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature