The Importance of the Acyltransferase LYCAT on PI3K-Akt Signaling and Cancer Cell Proliferation

Phosphoinositides (PIPs) play a key role in regulating key cellular functions. PIPs are enriched with a unique acyl profile composed of stearate and arachidonate at the sn-1 and sn-2 positions, respectively, which is governed by phospholipase As and acyltransferases. Specifically, lysocardiolipin acyltransferase (LYCAT) incorporates stearic acid onto the sn-1 position. Previous work found that LYCAT silencing selectively perturbs the levels and localization of phosphatidylinositol-4,5-bisphosphate, an important precursor for phosphatidylinositol-3,4,5- trisphosphate (PIP3). PIP3 recruits and modulates the effector Akt, which promotes and coordinates cell survival and proliferation. Thus, we hypothesized that LYCAT is important in PIP3-Akt signaling and cell proliferation. Our results show that LYCAT silencing suppresses EGF- stimulated phosphorylation of Akt and select downstream substrates. Further, we observed impaired cell proliferation. Overall, our results suggest that the acyl specificity governed by LYCAT may play a significant role in controlling cell signaling and proliferation, which may have consequences for diseases such as cancer.