LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer

• DOI: 10.1186/s13046-018-0947-4
• Publication Date: 2018-11-12T08:58:26Z
• Authors: Mengyu Feng; Guangbing Xiong; Zhe Cao; Gang Yang; Suli Zheng; Jiangdong Qiu; Lei You; Lianfang Zheng; Taiping Zhang; Yupei Zhao
• Keywords: Amino acid transporter

Reprogrammed energy metabolism has become an emerging hallmark of cancer in recent years. Transporters have been reported to be amino acid sensors involved controlling mTOR recruitment and activation, which is crucial for the growth both normal tumor cells. L-type transporter 2 (LAT2), encoded by SLC7A8 gene, a Na+-independent neutral responsible transporting acids, including glutamine, can activate mTOR. Previous studies shown that LAT2 was overexpressed gemcitabine-resistant pancreatic However, role chemoresistance remains uncertain elusive. The effects on biological behaviors were analyzed. LDHB levels tissues detected, clinical value evaluated. We demonstrated emerged as oncogenic protein could decrease gemcitabine sensitivity cells vitro vivo. results survival analysis indicated high expression predicted poor prognosis patients with cancer. Furthermore, we found promote proliferation, inhibit apoptosis, glycolysis alter glutamine Next, combined inhibitor (RAD001) reverse chemosensitivity caused overexpression Mechanistically, regulate two glutamine-dependent positive feedback loops (the LAT2/p-mTORSer2448 loop glutamine/p-mTORSer2448/glutamine synthetase loop) (GEM) Taken together, our data reveal functions activation GEM LAT2-mTOR-LDHB pathway might promising therapeutic target