Inhibition of lysophosphatidic acid acyltransferase beta disrupts proliferative and survival signals in normal cells and induces apoptosis of tumor cells.

Lysophosphatidic acid acyltransferase beta (LPAAT-beta) is an intrinsic membrane protein that catalyzes the synthesis of phosphatidic acid (PA) from lysoPA. Given that PA is a cofactor in a number of signaling cascades that are constitutively active in tumors, we evaluated the role of PA produced by LPAAT-beta in Xenopus oocyte meiotic maturation assays and an isoform-specific inhibitor of LPAAT-beta in mammalian cell assays. We found that ectopic overexpression of LPAAT-beta cooperates in activation of the Ras/Raf/Erk pathway in Xenopus oocytes and that inhibition of LPAAT-beta inhibits signaling in both the Ras/Raf/Erk and PI3K/Akt pathways.