NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells

Yanchao Mu, Xiaojie Yan, Ding Li, Dan Zhao, Lingling Wang, Xiaoyang Wang, Dan Gao, Jie Yang, Hua Zhang, Yanzhe Li, Yanan Sun, Yiliang Wei, Zhenfa Zhang, Xinzhong Chang, Zhi Yao, Shanshan Tian, Kai Zhang, Lance S. Terada, Zhenyi Ma, Zhe Liu

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE-associated protein VAMP8. NUPR1 depletion deregulates autophagic flux and impairs autolysosomal clearance, inducing massive cytoplasmic vacuolization and premature senescence in vitro and tumor suppression in vivo. Collectively, our data show that NUPR1 is a potent regulator of autolysosomal dynamics and is required for the progression of some epithelial cancers.

Original languageEnglish (US)
Pages (from-to)654-670
Number of pages17
JournalAutophagy
Volume14
Issue number4
DOIs
StatePublished - Apr 3 2018

Keywords

  • NUPR1
  • SNAP25
  • autolysosomal efflux
  • premature senescence
  • transcriptional regulator

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Mu, Y., Yan, X., Li, D., Zhao, D., Wang, L., Wang, X., Gao, D., Yang, J., Zhang, H., Li, Y., Sun, Y., Wei, Y., Zhang, Z., Chang, X., Yao, Z., Tian, S., Zhang, K., Terada, L. S., Ma, Z., & Liu, Z. (2018). NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells. Autophagy, 14(4), 654-670. https://doi.org/10.1080/15548627.2017.1338556