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

被引：516

作者：

Steelman, Linda S. ^{[1
,2
]}

Chappell, William H. ^{[1
]}

Abrams, Stephen L. ^{[1
]}

Kempf, C. Ruth ^{[2
]}

Long, Jacquelyn ^{[2
]}

Laidler, Piotr ^{[3
]}

Mijatovic, Sanja ^{[4
]}

Maksimovic-Ivanic, Danijela ^{[4
]}

Stivala, Franca ^{[5
]}

Mazzarino, Maria C. ^{[5
]}

Donia, Marco ^{[5
]}

Fagone, Paolo ^{[5
]}

Malaponte, Graziella ^{[5
]}

Nicoletti, Ferdinando ^{[5
]}

Libra, Massimo ^{[5
]}

Milella, Michele ^{[6
]}

Tafuri, Agostino ^{[7
]}

Bonati, Antonio ^{[8
]}

Baesecke, Joerg ^{[9
]}

Cocco, Lucio ^{[10
]}

Evangelisti, Camilla ^{[10
]}

Martelli, Alberto M. ^{[10
,11
]}

Montalto, Giuseppe ^{[12
]}

Cervello, Melchiorre ^{[13
]}

McCubrey, James A. ^{[1
]}

机构：

[1] E Carolina Univ, Dept Microbiol & Immunol, Greenville, NC 27858 USA

[2] E Carolina Univ, Dept Phys, Greenville, NC 27858 USA

[3] Jagiellonian Univ, Coll Med, Dept Med Biochem, Krakow, Poland

[4] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Dept Immunol, Belgrade, Serbia

[5] Univ Catania, Dept Biomed Sci, Catania, Italy

[6] Regina Elena Canc Ctr, I-00144 Rome, Italy

[7] Univ Roma La Sapienza, Dept Hematol Oncol, I-99161 Rome, Italy

[8] Univ Hosp Parma, Unit Hematol & Bone Marrow Transplantat, I-43100 Parma, Italy

[9] Univ Gottingen, Dept Med, Gottingen, Germany

[10] Univ Bologna, Dipartimento Sci Anat Umane & Fisiopatol Apparat, Bologna, Italy

[11] IOR, IGM CNR, Sez Bologna, Bologna, Italy

[12] Univ Palermo, Dept Internal Med & Specialties, Palermo, Italy

[13] Ist Biomed & Immunol, Consiglio Nazl Ric, Palermo, Italy

来源：

AGING-US | 2011年 / 3卷 / 03期

关键词：

Raf; MEK; PI3K; mTOR; cancer; kinases; protein phosphorylation; signal transduction; apoptosis; HEPATITIS-C-VIRUS; SUPPRESSOR GENE PTEN/MMAC1; SIGNAL-REGULATED KINASES; CELL-CYCLE PROGRESSION; ACUTE MYELOID-LEUKEMIA; CAP-BINDING PROTEIN; NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; STEM-CELLS; RIBOSOMAL-PROTEIN;

D O I：

10.18632/aging.100296

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：192 / 222

页数：31

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