LKB1/AMPK/mTOR signaling pathway in hematological malignancies: From metabolism to cancer cell biology

Abstract

The link between cancer and metabolism has been suggested for a long time but further evidence of this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis. Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. Notably, most of experimental evidence of the anti-tumor activity of AMPK agonists comes from the study of solid tumors such as breast or prostate cancers and only few data are available in hematological malignancies, although recent works emphasized the potential therapeutic value of AMPK agonists in this setting. Further basic research work should be conducted to elucidate the molecular targets of LKB1/AMPK responsible for its anti-tumor activity in parallel of conducting clinical trials using metformin, AICAR or new AMPK activating agents to explore the potential of the LKB1/AMPK signaling pathway as a new target for anticancer drug development. © 2011 Landes Bioscience.