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PLCε regulates metabolism and metastasis signaling via HIF‐1α/MEK/ERK pathway in prostate cancer
Author(s) -
Fan Yanru,
Ou Liping,
Fan Jiaxin,
Li Luo,
Wang Xiao,
Niu Lingfang,
Wu Xiaohou,
Luo Chunli
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29698
Subject(s) - gene knockdown , carcinogenesis , metastasis , cancer research , signal transduction , prostate cancer , biology , mapk/erk pathway , phospholipase c , ubiquitin ligase , microbiology and biotechnology , cancer , cell culture , ubiquitin , biochemistry , gene , genetics
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.