Although elevated expression of CAV1/caveolin 1 is associated with the malignant progression of various human cancers, the molecular mechanism underlying its oncogenic functions is largely unknown. We found that CAV1 is frequently overexpressed in advanced colorectal tumors due to aberrant promoter CpG site hypomethylation, and its elevation is implicated in enhanced aerobic glycolysis of tumor cells. Depletion of elevated CAV1 downregulates glucose uptake, intracellular ATP level and lactate accumulation, and triggers autophagy through activation of AMPK-TP53/p53 signaling. CAV1 elevation increases glucose uptake and ATP production by stimulating transcription of the glucose transporter SLC2A3/GLUT3 via an HMGA1-binding site within the promoter. Collectively, our study suggests that elevated CAV1 expression may contribute to colorectal tumor progression by providing tumor cells growth and survival advantages under nutritional stress conditions.
Keywords: GLUT3; HMGA1; autophagy; caveolin-1; colon cancer; glycolysis.