PI3K/AKT/mTOR通路
雷氏菌
蛋白激酶B
RPTOR公司
PTEN公司
癌症研究
细胞生物学
TSC1
mTORC1型
自噬
生物
P70-S6激酶1
mTORC2型
受体酪氨酸激酶
磷酸化
信号转导
遗传学
细胞凋亡
作者
Masahiro Aoki,Teruaki Fujishita
出处
期刊:Current Topics in Microbiology and Immunology
日期:2017-01-01
卷期号:: 153-189
被引量:315
摘要
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP. Possible mechanisms by which the PI3K/AKT/mTOR axis contributes to oncogenic transformation include stimulation of proliferation, survival, metabolic reprogramming, and invasion/metastasis, as well as suppression of autophagy and senescence. These phenotypic changes are mediated by eIF4E-induced translation of a subset of mRNAs and by other downstream effectors of mTORC1 including S6K, HIF-1α, PGC-1α, SREBP, and ULK1 complex.
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