PLCε regulates metabolism and metastasis signaling via HIF-1α/MEK/ERK pathway in prostate cancer.

Abstract:

:Phospholipase C-ε (PLCε) is frequently overexpressed in tumors and plays an important role in the regulation of tumorigenesis. Although great progress has been made in understanding biological roles of PLCε, the relevant molecular mechanisms underlying its pro-tumor activity remain largely unclear. Here, we demonstrated that PLCε knockdown reduced cell metastasis, glucose consumption and lactate production in a manner that depended on hypoxia inducible factor 1α (HIF-1α) expression in prostate cancer cells. Interestingly, our findings showed that the expression levels of PLCε were positively associated with those of HIF-1α in clinical prostate carcinoma samples. Knockdown of PLCε impaired HIF-1α levels and transcriptional activity by regulating the extracellular-signal-regulated kinase pathway, and blocking HIF-1α nuclear translocation. Furthermore, PLCε could interact with the von Hippel-Lindau E3 ligase complex to modulate the stability of HIF-1α. Collectively, our findings demonstrate that PLCε could be a crucial positive regulator of HIF-1α, which would promote PLCε-enhanced tumorigenesis.

journal_name

J Cell Physiol

authors

Fan Y,Ou L,Fan J,Li L,Wang X,Niu L,Wu X,Luo C

doi

10.1002/jcp.29698

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

8546-8557

issue

11

eissn

0021-9541

issn

1097-4652

journal_volume

235

pub_type

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