TY - JOUR
T1 - Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging
AU - Steelman, Linda S.
AU - Chappell, William H.
AU - Abrams, Stephen L.
AU - Kempf, C. Ruth
AU - Long, Jacquelyn
AU - Laidler, Piotr
AU - Mijatovic, Sanja
AU - Maksimovic-Ivanic, Danijela
AU - Stivala, Franca
AU - Mazzarino, Maria C.
AU - Donia, Marco
AU - Fagone, Paolo
AU - Malaponte, Graziella
AU - Nicoletti, Ferdinando
AU - Libra, Massimo
AU - Milella, Michele
AU - Tafuri, Agostino
AU - Bonati, Antonio
AU - Bäsecke, Jörg
AU - Cocco, Lucio
AU - Evangelisti, Camilla
AU - Martelli, Alberto M.
AU - Montalto, Giuseppe
AU - Cervello, Melchiorre
AU - McCubrey, James A.
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cancer
KW - Kinases
KW - MEK
KW - MTOR
KW - PI3K
KW - Protein phosphorylation
KW - RAF
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=79961173138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961173138&partnerID=8YFLogxK
M3 - Article
C2 - 21422497
AN - SCOPUS:79961173138
VL - 3
SP - 192
EP - 222
JO - Aging
JF - Aging
SN - 1945-4589
IS - 3
ER -