title: Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging.
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.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27858, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Steelman
authors.forename: William H
authors.initials: WH
authors.lastname: Chappell
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Abrams
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Kempf
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Long
authors.forename: Piotr
authors.initials: P
authors.lastname: Laidler
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatovic
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimovic-Ivanic
authors.forename: Franca
authors.initials: F
authors.lastname: Stivala
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mazzarino
authors.forename: Marco
authors.initials: M
authors.lastname: Donia
authors.forename: Paolo
authors.initials: P
authors.lastname: Fagone
authors.forename: Graziella
authors.initials: G
authors.lastname: Malaponte
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Agostino
authors.initials: A
authors.lastname: Tafuri
authors.forename: Antonio
authors.initials: A
authors.lastname: Bonati
authors.forename: Jörg
authors.initials: J
authors.lastname: Bäsecke
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Camilla
authors.initials: C
authors.lastname: Evangelisti
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016922:Cellular Senescence; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism
chemical_list: D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048490:raf Kinases; C546842:MTOR protein, human; C494929:PTEN protein, human