Dataset Information

A regulatory axis of YY1-PFKP promotes aggressive prostate tumorigenesis via potentiating tumor cell metabolism [ChIP-seq]

ABSTRACT: Yin Yang 1 (YY1) acts as a transcription factor crucially involved in cell proliferation, differentiation and survival. We here report that YY1, through gene expression regulation, plays an important role in prostate tumorigenesis, notably in castration-resistant prostate cancer (CRPC) models. Specifically, we found that YY1 displays a significantly elevated level among primary samples from prostate cancer patients, relative to normal. Depletion of YY1 in multiple independent prostate cancer model systems dramatically reduced tumor cell growth in vitro and significantly delayed oncogenic progression in vivo. Using integrated analyses of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq), we further defined YY1-regulated cistrome, among which include a set of metabolism-related genes such as PFKP (Phosphofructokinase, Platelet isoform), a rate-limiting enzyme essential for glycolysis. Via both gene loss-of-function and rescue studies, we demonstrate that PFKP serves as a key downstream direct target of YY1, significantly contributing to YY1-enforced oncogenic phenotypes such as enhanced tumor cell glycolysis and prostate cancer growth. Lastly, we show that BRD4, a cofactor of YY1, is critically involved in YY1-mediated activation of metabolic genes in prostate cancer cells. Altogether, this study unveils an oncogenic axis of YY1/BRD4-PFKP in prostate cancer for potentiating more aggressive tumor characteristics, which shall shed light on targeted therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153639 | GEO | 2021/06/03

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of PFKP (phosphofructokinase, platelet), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of PFKP (phosphofructokinase, platelet), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.

Dataset Information

A regulatory axis of YY1-PFKP promotes aggressive prostate tumorigenesis via potentiating tumor cell metabolism [ChIP-seq]

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure