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.

• Authors: Yanru Fan, Liping Ou, Jiaxin Fan, Luo Li, Xiao Wang, Lingfang Niu, Xiaohou Wu, Chunli Luo
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 235 Issue 11 Pg. 8546-8557 (11 2020) ISSN: 1097-4652 [Electronic] United States
• PMID: 32383180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Vascular Endothelial Growth Factor A
• Extracellular Signal-Regulated MAP Kinases
• Phosphoinositide Phospholipase C
• phospholipase C epsilon

Topics

• Cell Line, Tumor
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Neoplasm Metastasis (pathology)
• Phosphoinositide Phospholipase C (metabolism)
• Prostatic Neoplasms (metabolism)
• Signal Transduction (physiology)
• Vascular Endothelial Growth Factor A (metabolism)