Lactate Facilitates the Survival and Invasion of Pancreatic Cancer Cells Under Glucose Deprivation

Lactate has been considered as a tumor-promoting metabolite, however, its functional roles in pancreatic cancer (PC) have not yet been fully elucidated. Here, we explored the roles of lactate on the proliferation and invasion of PC cells under glucose deprivation. We found that lactate enhanced PC cells' proliferation and invasion under glucose deprivation, but not in normal conditions. The Cancer Genome Atlas (TCGA) Pancreatic Adenocarcinoma (PAAD) dataset showed that monocarboxylic acid transporter 1 (MCT1), a lactate transporter, was overexpressed and correlated with poor prognosis in PC patients. Additionally, knockdown or inhibition of MCT1 distinctively attenuated lactate-induced proliferation and invasion of PC cells under glucose deprivation by suppressing their tricarboxylic acid (TCA) cycle. Importantly, the MCT1 inhibitor AZD3965 synergistically enhanced the anticancer effects of the glycolysis inhibitor 2-DG. Taken together, our results demonstrate that MCT1-mediated lactate influx sustains PC proliferation under glucose starvation, and combined inhibition of MCT1 and glycolysis could be leveraged for treatment of PC.