Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma

J Transl Med. 2022 Jan 28;20(1):47. doi: 10.1186/s12967-022-03247-4.

Abstract

Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.

Keywords: Development; EGFR; Lung adenocarcinoma; NEDD4L; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • Nedd4 Ubiquitin Protein Ligases
  • Signal Transduction

Substances

  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4L protein, human
  • EGFR protein, human
  • ErbB Receptors