Abstract：
: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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Cai J,Li R,Xu X,Zhang L,Lian R,Fang L,Huang Y,Feng X,Liu X,Li X,Zhu X,Zhang H,Wu J,Zeng M,Song E,He Y,Yin Y,Li J,Li Mdoi
10.1038/s41556-018-0065-8subject
Has Abstractpub_date
2018-04-01 00:00:00pages
465-478issue
4eissn
1465-7392issn
1476-4679pii
10.1038/s41556-018-0065-8journal_volume
20pub_type
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