Review Volume 3, Issue 3 pp 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
- 1 Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27858, USA
- 2 Department of Physics, East Carolina University, Greenville, NC 27858, USA
- 3 Department of Medical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
- 4 Department of Immunology, Instititue for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia
- 5 Department of Biomedical Sciences, University of Catania, Catania, Italy
- 6 Regina Elena Cancer Center, Rome 00144, Italy
- 7 University of Rome, La Sapienza, Department of Hematology-Oncology, Rome 99161, Italy
- 8 University Hospital of Parma, Unit of Hematology and Bone-Marrow Transplantation, Via Gramsi n.14, Parma 43100, Italy
- 9 Department of Medicine, University of Göttingen, Göttingen, Germany
- 10 Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Università di Bologna, Bologna, Italy
- 11 IGM-CNR, Sezione di Bologna, C/o IOR, Bologna, Italy
- 12 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy
- 13 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia, Molecolare “Alberto Monroy”, Palermo, Italy
Received: February 25, 2011 Accepted: March 10, 2011 Published: March 10, 2011
https://doi.org/10.18632/aging.100296How to Cite
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.