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Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging |
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| Authors: | Steelman Linda S Chappell William H Abrams Stephen L Kempf Ruth C Long Jacquelyn Laidler Piotr Mijatovic Sanja Maksimovic-Ivanic Danijela Stivala Franca Mazzarino Maria C Donia Marco Fagone Paolo Malaponte Graziella Nicoletti Ferdinando Libra Massimo Milella Michele Tafuri Agostino Bonati Antonio Bäsecke Jörg Cocco Lucio Evangelisti Camilla Martelli Alberto M Montalto Giuseppe Cervello Melchiorre McCubrey James A |
| Affiliation: | Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27858, USA. |
| Abstract: | Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health. |
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