AMPK as a metabolic tumor suppressor: control of metabolism and cell growth.
AMPK is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for metabolic syndrome and Type 2 diabetes. Recent studies indicate that AMPK plays a role in linking metabolic syndrome and cancer. AMPK is an essential mediator of the tumor suppressor LKB1 and could be suppressed in cancer cells containing loss-of-function mutations of LKB1 or containing active mutations of B-Raf, or in cancers associated with metabolic syndrome. The activation of AMPK reprograms cellular metabolism and enforces metabolic checkpoints by acting on mTORC1, p53, fatty acid synthase and other molecules for regulating cell growth and metabolism. In keeping with in vitro studies, recent epidemiological studies indicate that the incidence of cancer is reduced in Type 2 diabetes treated with metformin, an AMPK activator. Thus, AMPK is emerging as an interesting metabolic tumor suppressor and a promising target for cancer prevention and therapy.
Luo
Zhijun
Z
Department of Biochemistry, Boston University School of Medicine, MA 02118, USA. zluo@bu.edu
Zang
Mengwei
M
Guo
Wen
W
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D049109:Cell Proliferation; D004734:Energy Metabolism / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D011494:Protein Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases