Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

Linda S Steelman, William H Chappell, Stephen L Abrams, Ruth C Kempf, Jacquelyn Long, Piotr Laidler, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Franca Stivala, Maria C Mazzarino, Marco Donia, Paolo Fagone, Graziella Malaponte, Ferdinando Nicoletti, Massimo Libra, Michele Milella, Agostino Tafuri, Antonio Bonati, Jörg Bäsecke, Lucio Cocco, Camilla Evangelisti, Alberto M Martelli, Giuseppe Montalto, Melchiorre Cervello, James A McCubrey
Aging 2011, 3 (3): 192-222
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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