The tumor suppressive function of AMPK in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. However, the molecular mechanism underlying the development of HCC is still unclear. AMP-activated protein kinase (AMPK), which is a serine/theronine protein kinase, originally found as a key regulator in glucose and lipid metabolism in response to cellular stress. Recent publications suggest that AMPK activation results in suppressing cell proliferation. Also, AMPK lies upstream and downstream of two tumor suppressors, TSC2 and LKB1, respectively, indicating that AMPK may also involve in carcinogenesis. In this project, we aim to study the molecular mechanism leading to the tumor suppressive function of AMPK in HCC, particularly relating to the p53 pathway. Our preliminary findings have shown that overexpression of AMPKα2 catalytic subunit in HCC cell line HepG2 suppress cell proliferation in focus formation assay. On the other hand, an increase in proliferation rate was observed in HCC cell with AMPKα2 stably knocked down by small hairpin RNA. Also, our data have demonstrated that expression of constitutive active form of AMPKα2 leads to p53 phosphorylation at serine 15 residue and acetylation at lysine 382 residue. In addition, in-vitro kinase assay has shown that AMPK directly phosphorylates p53. Our results suggest that AMPK may mediate its tumor suppression function through regulation of p53.