AMPK: a contextual oncogene or tumor suppressor?

The AMP-activated protein kinase (AMPK) functions to monitor and maintain energy homeostasis at the cellular and organism level. AMPK was perceived historically primarily as a component of the LKB1/STK11 tumor suppressor (LKB1 mutations cause the Peutz-Jegher cancer predisposition syndrome) cascade upstream of the TSC1/2/mTOR pathway and thus likely to be a tumor suppressor. However, AMPK has recently been shown to promote cancer cell survival in the face of extrinsic and intrinsic stressors including bioenergetic, growth factor, and oncogene stress compatible with studies showing that AMPK is required for oncogenic transformation. Thus, whether AMPK acts as a bona fide tumor suppressor or a contextual oncogene and, of particular importance, whether AMPK should be targeted for activation or inhibition during cancer therapy, is controversial and requires clarification. We aim to initiate discussions of these critical questions by reviewing the role of AMPK with an emphasis on cancer cell adaptation to microenvironment stress and therapeutic intervention.