AMP-activated protein kinase β1 or β2 deletion enhances colon cancer cell growth and tumorigenesis.

Abstract

Abnormal metabolism is a major hallmark of cancer and has been validated as a therapeutic target. Adenine monophosphate-activated protein kinase (AMPK), an αβγ heterotrimer, performs essential functions in cancer progression due to its central role in maintaining the homeostasis of cellular energy. While the contributions of AMPKα and AMPKγ subunits to cancer development have been established, specific roles of AMPKβ1 and AMPKβ2 isoforms in cancer development are poorly understood. Here, we show the functions of AMPKβ1 and AMPKβ2 in colon cancer. Specifically, deletion of AMPKβ1 or AMPKβ2 leads to increased cell proliferation, colony formation, migration, and tumorigenesis in HCT116 and HT29 colon cancer cells. Interestingly, the AMPKβ1 and AMPKβ2 isoforms have slightly different effects on regulating cancer metabolism, as colon cancer cells with AMPKβ1 knockout showed decreased rates of glycolysis-related oxygen consumption, while AMPKβ2 deletion led to enhanced rates of oxygen consumption due to oxidative phosphorylation. These results demonstrate that functional AMPKβ1 and AMPKβ2 inhibit growth and tumorigenesis in colon cancer cells, suggesting their potential as effective targets for colon cancer therapy.