PTEN公司
自噬
酪蛋白激酶1
蛋白激酶B
癌变
癌症研究
PI3K/AKT/mTOR通路
细胞生长
肺癌
生物
磷酸化
细胞生物学
信号转导
细胞凋亡
癌症
医学
蛋白激酶A
内科学
生物化学
遗传学
作者
Junchao Cai,Rong Li,Xiaonan Xu,Le Zhang,Rong Lian,Lishan Fang,Yongbo Huang,Xianming Feng,Ximeng Liu,Li Xu,Xun Zhu,Heng Zhang,Jueheng Wu,Mu‐Sheng Zeng,Erwei Song,Yukai He,Yuxin Yin,Jun Li,Mengfeng Li
标识
DOI:10.1038/s41556-018-0065-8
摘要
The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7. Notably, blocking CK1α-induced Atg7-dependent autophagy cooperates with oncogenic HRasV12 to initiate tumorigenesis of lung epithelial cells. An association of a CK1α-modulated autophagic program with the anti-neoplastic activities of the CK1α/PTEN/FOXO3a/Atg7 axis was demonstrated in xenografted tumour models and human NSCLC specimens. This provides insights into the biological and potentially clinical significance of autophagy in NSCLC.
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