Metastasis remains the major cause of death from
colon cancer. We intend to identify differentially expressed genes that are associated with the metastatic process and prognosis in
colon cancer.
ATP synthase epsilon subunit (ATP5E) gene was found to encode the mitochondrial F0F1
ATP synthase subunit epsilon that was overexpressed in
tumor cells compared to their normal counterparts, while other genes encoding the
ATP synthase subunit were repressed in public microarray datasets. CRC cells in which ATP5E was silenced showed markedly reduced invasive and migratory abilities. ATP5E inhibition significantly reduced the incidence of distant
metastasis in a mouse xenograft model. Mechanistically, increased ATP5E expression resulted in a prominent reduction in
E-cadherin and an increase in Snail expression. Our data also showed that an elevated ATP5E level in metastatic
colon cancer samples was significantly associated with the AMPK-AKT-
hypoxia-inducible factor-1α (HIF1α) signaling axis; silencing ATP5E led to the degradation of HIF1α under
hypoxia through AMPK-AKT signaling. Our findings suggest that elevated ATP5E expression could serve as a marker of distant
metastasis and a poor prognosis in
colon cancer, and ATP5E functions via modulating AMPK-AKT-HIF1α signaling.