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.

中文翻译：

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PLCε通过HIF-1α/ MEK / ERK途径调节前列腺癌的代谢和转移信号。

磷脂酶C-ε（PLCε）在肿瘤中经常过表达，并且在调节肿瘤发生中起重要作用。尽管在了解PLCε的生物学作用方面已取得了很大进展，但其促癌活性的相关分子机制仍不清楚。在这里，我们证明了PLCε敲低可以减少前列腺癌细胞中的低氧诱导因子1α（HIF-1α）表达，从而减少细胞转移，葡萄糖消耗和乳酸产生。有趣的是，我们的发现表明，临床前列腺癌样本中PLCε的表达水平与HIF-1α的表达呈正相关。抑制PLCε通过调节细胞外信号调节的激酶途径和阻断HIF-1α核易位而损害了HIF-1α的水平和转录活性。此外，PLCε可以与von Hippel–Lindau E3连接酶复合物相互作用，从而调节HIF-1α的稳定性。总的来说，我们的发现表明PLCε可能是HIF-1α的关键正调控因子，它将促进PLCε增强的肿瘤发生。