DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2.

ABSTRACT: Diacylglycerol kinase ζ (DGKZ) is a diacylglycerol kinase that metabolizes diacylglycerol to yield phosphatidic acid, and its function in breast cancer progression remains unclear. In this study, via screening of a CRISPR-Cas9 knockout library containing lipid metabolic genes, DGKZ was identified as a potential prometastatic gene. We first confirmed that high DGKZ expression correlated with tumor progression and poor prognosis in patients. Next, knockout of DGKZ in triple-negative breast cancer cell lines were found to significantly inhibit metastatic behaviors in vitro and in vivo, whereas its overexpression increased the metastatic potential of cell lines. Mechanistic studies based on RNA sequencing and bioinformatic analysis indicated that DGKZ might regulate cell metastasis by promotin

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8814002 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature