CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy

Junchao Cai, Rong Li, Xiaonan Xu, Le Zhang, Rong Lian, Lishan Fang, Yongbo Huang, Xianming Feng, Ximeng Liu, Xu Li, Xun Zhu, Heng Zhang, Jueheng Wu, Musheng Zeng, Erwei Song, Yukai He, Yuxin Yin, Jun Li, Mengfeng Li

Research output: Contribution to journalArticle

20 Scopus citations

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 HRas V12 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.

Original languageEnglish (US)
Pages (from-to)465-478
Number of pages14
JournalNature Cell Biology
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2018

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    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, M. (2018). CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy. Nature Cell Biology, 20(4), 465-478. https://doi.org/10.1038/s41556-018-0065-8