title: Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence.
abstract: Oncogene-induced senescence (OIS) is a tumor-suppressing response that must be disrupted for cancer to develop. Mechanistic insights into OIS have begun to emerge. Activation of the p53/p21(WAF1) and/or p16(INK4A) tumor-suppressor pathways is essential for OIS. Moreover, the DNA damage response, chromatin remodeling, and senescence-associated secretory phenotype (SASP) are important for the initiation and maintenance of OIS. This review discusses recent advances in elucidating the mechanisms of OIS, focusing on the roles of the p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/cellular homolog of murine thymoma virus AKT/mammalian target of rapamycin (mTOR) pathways. These studies indicate that OIS is mediated by an intricate signaling network. Further delineation of this network may lead to development of new cancer therapies targeting OIS.
authors.affiliation: College of Medicine, Nankai University, 94 Weijin Road, Tianjin, China, 300071; Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Medicine, Nankai University, 94 Weijin Road, Tianjin, China, 300071.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: College of Medicine, Nankai University, 94 Weijin Road, Tianjin, China, 300071.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: pqsun@scripps.edu.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: AKT; oncogene-induced senescence; p38; phosphoinositide 3-kinase