AKT and cytosolic phospholipase A₂α form a positive loop in prostate cancer cells

Title:AKT and cytosolic phospholipase A₂α form a positive loop in prostate cancer cells

Volume: 15 Issue: 9

Author(s): Sheng Hua, Soma Vignarajan, Mu Yao, Chanlu Xie, Paul Sved and Qihan Dong

Affiliation:

Keywords: AKT, AR, cPLA₂α, ERK, PI3K, prostate cancer, PTEN.

Abstract: Aberrant increase in protein kinase B (AKT) phosphorylation (pAKT), due to a gain-of-function mutation of phosphatidylinositol-3-kinase (PI3K) or loss-of-function mutation or deletion of phosphatase and tensin homolog (PTEN), is a common alteration in prostate cancer and associated with poor prognosis. Cytosolic phospholipase A2α (cPLA₂α) is a lipid modifying enzyme by catalyzing the hydrolysis of arachidonic acid from membrane phospholipid. The released arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. In this mini-review, we summarize the relationship between pAKT and cPLA₂α in prostate cancer cells. There was a concordant increase in pAKT and cPLA₂α levels in prostate tissue of prostate epithelial-specific PTEN-knockout mice compared to PTEN-wild type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA₂α expression in PTEN-mutated or deleted prostate cancer cells. An increase in AKT phosphorylation elevated, whereas inhibition of AKT phosphorylation diminished, cPLA₂α protein levels. pAKT had no influence on cPLA₂α expression at mRNA levels but stabilized cPLA2α at protein levels by protecting it from degradation. Conversely, an induction of cPLA₂α expression led to an increase in pAKT levels in PTEN-mutated or deleted prostate cancer cells, while silencing of cPLA₂α expression or pharmacological blocking cPLA₂α action decreased pAKT levels. The diminishment of pAKT by either genetic silencing or pharmacological blocking of cPLA₂α was mitigated by the addition of arachidonic acid. The stimulatory effect of arachidonic acid on pAKT levels was lessened by inhibiting the production of arachidonic acid metabolites. These studies have revealed a link between oncogenic pathway and lipid metabolism and provided potential molecular targets for treating prostate cancer.

Cite this article as:

Hua Sheng, Vignarajan Soma, Yao Mu, Xie Chanlu, Sved Paul and Dong Qihan, AKT and cytosolic phospholipase A₂α form a positive loop in prostate cancer cells, Current Cancer Drug Targets 2015; 15 (9) . https://dx.doi.org/10.2174/1568009615666150706103234