TRIP suppresses cell proliferation and invasion in choroidal melanoma via promoting the proteasomal degradation of Twist1

FEBS Lett. 2020 Oct;594(19):3170-3181. doi: 10.1002/1873-3468.13882. Epub 2020 Sep 21.

Abstract

Choroidal melanoma (CM) remains the most prevalent form of intraocular malignancy, and the prognosis of affected patients is poor. While the E3 ubiquitin ligase TRAF-interacting protein (TRIP) is known to play key regulatory roles in multiple diseases, its relevance in CM remains uncertain. In the present study, we found that TRIP overexpression is sufficient to inhibit the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of CM cells in vitro, whereas the opposite phenotypes are observed following TRIP knockdown. We further determined that TRIP is able to promote the K48-polyubiquitination of EMT-associated transcription factor Twist-related protein 1, thereby suppressing EMT progression. Together, our results suggest that TRIP plays an important role in regulating the progression of CM and that it may therefore be an important therapeutic target for the treatment of this disease.

Keywords: EMT; TRIP; Twist1; choroidal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Choroid / pathology*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lysine / metabolism
  • Melanoma / genetics
  • Melanoma / pathology*
  • Neoplasm Invasiveness
  • Polyubiquitin / metabolism
  • Prognosis
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis*
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Up-Regulation / genetics

Substances

  • Twist-Related Protein 1
  • Polyubiquitin
  • TRAIP protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex
  • Lysine