Cell Communication and Signaling (Aug 2022)

GNIP1 functions both as a scaffold protein and an E3 ubiquitin ligase to regulate autophagy in lung cancer

  • Feifei Zhou,
  • Yufeng Liu,
  • Wenqian Ai,
  • Yanan Wang,
  • Mingxi Gan,
  • Qingkun Jiang,
  • Tianyu Han,
  • Jian-Bin Wang

DOI
https://doi.org/10.1186/s12964-022-00936-x
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 18

Abstract

Read online

Abstract Background Glycogen-Interacting Protein 1 (GNIP1), an E3 ligase, is a member of the tripartite motif (TRIM) family proteins. Current studies on GNIP1 mainly focus on glycogen metabolism. However, the function and molecular mechanisms of GNIP1 in regulating autophagy still remains unclear. This study aimed to investigate the regulatory mechanism of GNIP1 in regulating autophagy in non-small cell lung cancer (NSCLC). Methods Crystal violet staining assays were used to evaluate the ability of cell growth and proliferation. Transwell and scratch wound healing assays were used to evaluate the cell migration ability. The protein expressions were measured by western blot and immunohistochemistry. Co-immunoprecipitation assays determined the protein–protein interactions. The in vivo effect of GNIP1 on tumor growth was determined by xenograft assay. Results We found that GNIP1 was overexpressed in tumor tissues and the expression level of GNIP1 was related to the poor prognosis and the survival time of NSCLC patients. In non-small cell lung cancer (NSCLC), GNIP1 increased proliferation and migration of cancer cells by promoting autophagy. Mechanistic studies indicated that GNIP1, as a scaffold protein, recruited BECN1 and LC3B to promote the formation of autophagosomes. Besides, GNIP1 mediated the degradation of 14-3-3ζ, the negative regulator of VPS34 complex, thus promoting autophagy. Overexpressing GNIP1 promoted tumorigenesis and enhanced autophagy in xenograft models. Conclusion GNIP1 promotes proliferation and migration of NSCLC cells through mediating autophagy, which provides theoretical basis for targeting GNIP1 as anti-cancer drugs. Video Abstract

Keywords