Dysregulation of mTOR activity through LKB1 inactivation

• Type of Material: Article
• Authors: Wei Zhou, Emory University; Adam I Marcus, Emory University; Paula M Vertino, Emory University
• Language: English
• Date: 2013
• Publisher: Sun Yat-sen University Cancer Center
• Publication Version: Final Published Version
• Copyright Statement: © Chinese Journal of Cancer
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.cjcsysu.cn/abstract.asp?fr=doi&idno=20585
• Title of Journal or Parent Work: Chinese Journal of Cancer
• ISSN: 1000-467X
• Volume: 32
• Issue: 8
• Start Page: 427
• End Page: 433
• Grant/Funding Information: This work was supported by NIH Grant R01-CA140571 (to W.Z.) and P01-CA116676 (to W.Z. and P.V.); W.Z. is an Anise McDaniel Brock Scholar, Georgia Cancer Coalition Scholar, and American Cancer Research Scholar
• Keywords: protein translation; bi-allelic inactivation; metabolism; Energetic stress
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.