AKT/PKB signaling mechanisms in cancer and chemoresistance.
During the past decade, Akt (also known as protein kinase B, PKB) has been extensively studied. It regulates a variety of cellular processes by mediating extracellular (mitogenic growth factor, insulin and stress) and intracellular (altered tyrosine receptor kinases, Ras and Src) signals. Activation of Akt by these signals is via its pleckstrin homology (PH) domain binding to products of phosphatidylinositol 3-kinase (PI3K). This process is negatively regulated by a dual phosphatase PTEN tumor suppressor. Today, more than 30 Akt substrates have been identified. These phosphorylation events mediate the effects of Akt on cell survival, growth, differentiation, angiogenesis, migration and metabolism. Further, PI3K/PTEN/Akt pathway is frequently altered in many human malignancies and overexpression of Akt induces malignant transformation and chemoresistance. Thus, the Akt pathway is a major target for anti-cancer drug development. This review focuses on Akt signaling mechanism in oncogenesis and chemoresistance, and ongoing translational efforts to therapeutically target Akt.
Kim
Donghwa
D
Department of Pathology, University of South Florida College of Medicine and H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
Dan
Han C
HC
Park
Sungman
S
Yang
Lin
L
Liu
Qiyuan
Q
Kaneko
Satoshi
S
Ning
Jinying
J
He
Lili
L
Yang
Hua
H
Sun
Mei
M
Nicosia
Santo V
SV
Cheng
Jin Q
JQ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt