Invasive phenotype induced by low extracellular pH requires mitochondria dependent metabolic flexibility.

ABSTRACT: Metabolic reprogramming is required for tumors to meet the bioenergetic and biosynthetic demands of malignant progression. Numerous studies have established a causal relationship between oncogenic drivers and altered metabolism, most prominently aerobic glycolysis, which supports rapid growth and affects the tumor microenvironment. Less is known about how the microenvironment modulates cancer metabolism. In the present study, we found that low extracellular pH, a common feature of solid tumors, provoked PDAC cells to decrease glycolysis and become resistant to glucose starvation. This was accompanied by increased dependency on mitochondrial metabolism, in which long-chain fatty acids became a primary fuel source. Consistent with previous reports, low pH enhanced tumor cell invasiveness. A

SUBMITTER: Shin SC 

PROVIDER: S-EPMC9894376 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature