Diacylglycerol kinase α promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src.

ABSTRACT: Diacylglycerol kinase (DGK)α converts diacylglycerol to phosphatidic acid. This lipid kinase sustains survival, migration and invasion of tumor cells, with no effect over untransformed cells, suggesting its potential as a cancer-specific target. Nonetheless the mechanisms that underlie DGKα specific contribution to cancer survival have not been elucidated. Using three-dimensional (3D) colon and breast cancer cell cultures, we demonstrate that DGKα upregulation is part of the transcriptional program that results in Src activation in these culture conditions. Pharmacological or genetic DGKα silencing impaired tumor growth in vivo confirming its function in malignant transformation. DGKα-mediated Src regulation contributed to limit the effect of Src inhibitors, and its transcriptional upregul

SUBMITTER: Torres-Ayuso P 

PROVIDER: S-EPMC4259432 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature