HRD1 Promotes Non-small Cell Lung Carcinoma Metastasis by Blocking Autophagy-mediated MIEN1 Degradation

  • J Biol Chem. 2023 Apr 17;104723. doi: 10.1016/j.jbc.2023.104723.
Cheng Zeng  1 ,  Jing Guo  2 ,  Jiajia Wu  1 ,  Tiantian Che  1 ,  Xiaoping Huang  2 ,  Huawen Liu  3 ,  Zhenghong Lin  4
Affiliations
  • 1. School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China.
  • 2. Affiliated Three Gorges Central Hospital of Chongqing University, Chongqing, P. R. China.
  • 3. Affiliated Three Gorges Central Hospital of Chongqing University, Chongqing, P. R. China. Electronic address: [email protected].
  • 4. School of Life Sciences, Chongqing University, Chongqing 401331, P.R. China. Electronic address: [email protected].
PMID: 37075843 DOI: 10.1016/j.jbc.2023.104723
Abstract

Dysregulation of Autophagy has been implicated in the development of many diseases, including Cancer. Here, we revealed a novel function of the E3 ubiquitin Ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis by regulating Autophagy. Mechanistically, HRD1 inhibits Autophagy by promoting ATG3 ubiquitination and degradation. Additionally, a pro-migratory and invasive factor, MIEN1 (migration and invasion enhancer 1), was found to be autophagically degraded upon HRD1 deficiency. Importantly, both HRD1 and MIEN1 expression are upregulated and positively correlated in lung tumors. Based on these results, we proposed a novel mechanism of HRD1 function that the degradation of ATG3 protein by HRD1 leads to Autophagy inhibition and MIEN1 release, thus promoting NSCLC metastasis. Therefore, our findings provided new insights into the role of HRD1 in NSCLC metastasis and new therapeutic targets for lung Cancer treatment.

Keywords
ATG3; HRD1; MIEN1; NSCLC metastasis; autophagy.
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