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; Christian Kempf; Jacquelyn M. Long; Piotr Laidler; Sanja Mijatović; Danijela Maksimović‐Ivanić; Franca Stivala; María Clorinda Mazzarino; Marco Donia; Paolo Fagone; Graziella Malaponte; Ferdinando Nicoletti; Massimo Libra; Michèle Milella; Agostino Tafuri; Antonio Bonati; Jörg Bäsecke; Lucio Cocco; Camilla Evangelisti; Alberto M. Martelli; Giuseppe Montalto; Melchiorre Cervello; James A. McCubrey

doi:10.18632/aging.100296

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(East Carolina University), William H. Chappell(East Carolina University), Stephen L. Abrams(East Carolina University), Christian Kempf(East Carolina University), Jacquelyn M. Long(East Carolina University), Piotr Laidler(Jagiellonian University), Sanja Mijatović(University of Belgrade), Danijela Maksimović‐Ivanić(University of Belgrade), Franca Stivala(University of Catania), María Clorinda Mazzarino(University of Catania), Marco Donia(University of Catania), Paolo Fagone(University of Catania), Graziella Malaponte(University of Catania), Ferdinando Nicoletti(University of Catania), Massimo Libra(University of Catania), Michèle Milella, Agostino Tafuri(Sapienza University of Rome), Antonio Bonati(University of Parma), Jörg Bäsecke(University of Göttingen), Lucio Cocco(University of Bologna), Camilla Evangelisti(Istituto Ortopedico Rizzoli), Alberto M. Martelli(University of Bologna), Giuseppe Montalto(University of Palermo), Melchiorre Cervello(National Research Council), James A. McCubrey(East Carolina University)

Aging

March 10, 2011

10.18632/aging.100296

Cited by 700Open Access

Full Text

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.

Related Papers

No related papers found

Powered by citation graph analysis