The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator.
The AMP-activated protein kinase (AMPK) is a central regulator of cellular metabolism and energy homeostasis in mammalian tissues. Pertinent to cancer biology is the fact that AMPK is situated in the center of a signaling network involving established tumor suppressors including LKB1, TSC2 and p53. However, recent research suggests that AMPK can exert pro- or anti-tumorigenic roles in cancer depending on context. Loss of AMPK activity has been observed in several tumor types, and can cooperate with oncogenic drivers to reprogram tumor cell metabolism and enhance cell growth and proliferation. However, AMPK activation can also provide a growth advantage to tumor cells by regulating cellular metabolic plasticity, thus providing tumor cells the flexibility to adapt to metabolic stress. Here we discuss the contextual nature of the "two faces" of AMPK in cancer, and discuss the rationale and context for employing AMPK activators versus inhibitors for cancer therapy.
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
Brandon
B
Faubert
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
Emma E
EE
Vincent
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
Maya C
MC
Poffenberger
Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: russell.jones@mcgill.ca.
Russell G
RG
Jones
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001645:Biguanides / Q000494:pharmacology; D049109:Cell Proliferation; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000077005:Tuberous Sclerosis Complex 2 Protein; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D001645:Biguanides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
AMPK; HIF-1α; Tumor metabolism; Warburg effect; mTOR