LKB1/AMPK/mTOR Signaling Pathway in Non-small-cell Lung Cancer

• Published in: Asian Pacific journal of cancer prevention : APJCP Vol. 14; no. 7; pp. 4033 - 4039
• Main Authors: Han, Dong, Li, Shao-Jun, Zhu, Yan-Ting, Liu, Lu, Li, Man-Xiang
• Format: Journal Article
• Language: English
• Published: Thailand 01.01.2013
• Subjects: Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Molecular Targeted Therapy; Protein Kinases - chemistry; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1513-7368; 2476-762X
• DOI: 10.7314/APJCP.2013.14.7.4033

Links between cancer and metabolism have been suggested for a long time but compelling evidence for 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. In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells. Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC). In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC.