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1 September 2010
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Cover Image
Cover Image
The diagram reflects potential and known effects of the diabetes drug metformin (one of the most commonly used drugs in the world) on important molecular pathways of carcinogenesis in cells. The mammalian target of rapamycin (mTOR) exists in TOR complex 1 (TORC1) and TORC2. TORC1 controls cell growth through phosphorylating p70 S6 kinase (p70S6K) and 4E-binding protein 1 (4EBP1). Various inputs of TORC1 regulation appear to directly affect the TSC1–TSC2 complex, which controls activation of the Ras homologue enriched in brain (RHEB) protein that directly activates TORC1. Growth factor signaling (through phosphatidylinositol 3-kinase [PI3K]/Akt and extracellular signal-regulated kinase [ERK]/ribosomal S6 kinase [Rsk] signaling) and energy homeostasis (through AMP-activated protein kinase [AMPK]) directly phosphorylate TSC2. In vivo, metformin downregulates TORC1 possibly via both AMPK-dependent mechanisms and AMPK-independent mechanisms (dotted blue line from “Energy stress”) or via its effect of decreasing levels of circulating insulin and insulin-like growth factor (IGF), which decreases activation of the IGF-1 receptor (IGF-1R)/insulin receptor (IR), leading in turn to suppression of PI3K and Ras signaling. See articles by Memmott et al. (beginning on page 1066), Hosono et al. (beginning on page 1077), Pollak (beginning on page 1060), and Engelman and Cantley (beginning on page 1049) for more information.Close Modal - PDF Icon PDF LinkTable of Contents
ISSN 1940-6207
EISSN 1940-6215
Issue Sections
Perspectives
Review
Research Articles
Metformin Suppresses Colorectal Aberrant Crypt Foci in a Short-term Clinical Trial
Kunihiro Hosono; Hiroki Endo; Hirokazu Takahashi; Michiko Sugiyama; Eiji Sakai; Takashi Uchiyama; Kaori Suzuki; Hiroshi Iida; Yasunari Sakamoto; Kyoko Yoneda; Tomoko Koide; Chikako Tokoro; Yasunobu Abe; Masahiko Inamori; Hitoshi Nakagama; Atsushi Nakajima
Endothelin Receptor Type B Gene Promoter Hypermethylation in Salivary Rinses Is Independently Associated with Risk of Oral Cavity Cancer and Premalignancy
Kavita Malhotra Pattani; Zhe Zhang; Semra Demokan; Chad Glazer; Myriam Loyo; Steven Goodman; David Sidransky; Francisco Bermudez; Germain Jean-Charles; Thomas McCaffrey; Tapan Padhya; Joan Phelan; Silvia Spivakovsky; Helen Yoo Bowne; Judith D. Goldberg; Linda Rolnitzky; Miriam Robbins; A. Ross Kerr; David Sirois; Joseph A. Califano
UV Radiation Inhibits 15-Hydroxyprostaglandin Dehydrogenase Levels in Human Skin: Evidence of Transcriptional Suppression
Benjamin L. Judson; Akira Miyaki; Vikram D. Kekatpure; Baoheng Du; Patricia Gilleaudeau; Mary Sullivan-Whalen; Arash Mohebati; Sudhir Nair; Jay O. Boyle; Richard D. Granstein; Kotha Subbaramaiah; James G. Krueger; Andrew J. Dannenberg
Genome-Wide Catalogue of Chromosomal Aberrations in Barrett's Esophagus and Esophageal Adenocarcinoma: A High-Density Single Nucleotide Polymorphism Array Analysis
Jian Gu; Jaffer A. Ajani; Ernest T. Hawk; Yuanqing Ye; Jeffrey H. Lee; Manoop S. Bhutani; Wayne L. Hofstetter; Stephen G. Swisher; Kenneth K. Wang; Xifeng Wu
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