AMP-activated protein kinase (AMPK), an established metabolic stress sensor, has gained popularity in
cancer biology due to its ability to control cellular growth and mediate cell cycle checkpoints in
cancer cells in response to low energy levels. AMPK is a key effector of the
tumor suppressor liver
kinase B 1 (LKB1) which inhibits the cellular growth mediator
mammalian target of rapamycin (mTOR) and activates checkpoint mediators such as p53 and the
cyclin dependent kinase inhibitors p21(cip1) and p27(kip1). However, recent work describes a novel function for AMPK as a sensor of genomic stress and a participant of the DNA damage response (DDR) pathway. Ionizing radiation and
chemotherapy activate AMPK in
cancer cells to mediate signal transduction downstream of
ataxia telangiectasia mutated (ATM) to activate p53- p21(cip1)/p27(kip1) and inhibit mTOR. We discuss evidence on the transcriptional and post-translational regulation of AMPK by ionizing radiation and the role of the
enzyme as a mediator of chemo- and radiation sensitivity in epithelial
cancer cells. Furthermore, we review data on the participation of AMPK in cytokinesis and observations suggesting a physical association of this
enzyme with the mitotic apparatus. The evidence available to date suggests that AMPK is a point of convergence of metabolic and genomic stress signals, which (1) control the activity of growth mediators, (2) propagate DDR, and (3) mediate the anti-proliferative effects of common cytotoxic
cancer therapy such as radiation and
chemotherapy. This highlights the importance of targeting AMPK with novel
cancer therapeutics.