Chronic acidosis rewires cancer cell metabolism through PPARα signaling.

ABSTRACT: The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pH_e ) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pH_e , but not at acidic pH_e . Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulate

SUBMITTER: Rolver MG 

PROVIDER: S-EPMC10108231 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature