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; C. Ruth 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

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, C. Ruth 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 CoccoCamilla Evangelisti, Alberto M. Martelli, Giuseppe Montalto, Melchiorre Cervello, James A. McCubrey

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	192-222
Number of pages	31
Journal	Aging
Volume	3
Issue number	3
Publication status	Published - Mar 2011

Keywords

Apoptosis
Cancer
Kinases
MEK
MTOR
PI3K
Protein phosphorylation
RAF
Signal transduction

ASJC Scopus subject areas

Ageing
Cell Biology
Geriatrics and Gerontology

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Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M. C., Donia, M., Fagone, P., Malaponte, G., Nicoletti, F., Libra, M., Milella, M., Tafuri, A., Bonati, A., Bäsecke, J., ... McCubrey, J. A. (2011). Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging, 3(3), 192-222.

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. / Steelman, Linda S.; Chappell, William H.; Abrams, Stephen L.; Kempf, C. Ruth; 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.

In: Aging, Vol. 3, No. 3, 03.2011, p. 192-222.

Research output: Contribution to journal › Article › peer-review

Steelman, LS, Chappell, WH, Abrams, SL, Kempf, CR, Long, J, Laidler, P, Mijatovic, S, Maksimovic-Ivanic, D, Stivala, F, Mazzarino, MC, Donia, M, Fagone, P, Malaponte, G, Nicoletti, F, Libra, M, Milella, M, Tafuri, A, Bonati, A, Bäsecke, J, Cocco, L, Evangelisti, C, Martelli, AM, Montalto, G, Cervello, M & McCubrey, JA 2011, 'Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging', Aging, vol. 3, no. 3, pp. 192-222.

Steelman, Linda S. ; Chappell, William H. ; Abrams, Stephen L. ; Kempf, C. Ruth ; 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. / Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. In: Aging. 2011 ; Vol. 3, No. 3. pp. 192-222.

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