Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway

J Bioenerg Biomembr. 2021 Apr;53(2):213-222. doi: 10.1007/s10863-021-09872-w. Epub 2021 Jan 30.

Abstract

TRIM15 is a member of tripartite motif-containing protein (TRIM) protein family, which plays important roles in several cancers. The aim of the present study was to evaluate the role of TRIM15 in esophageal squamous cell carcinoma (ESCC). Our results showed that TRIM15 was upregulated in human ESCC tissues and cell lines. In vitro studies showed that knockdown of TRIM15 significantly inhibited the proliferation, migration, and invasion of ESCC cells. Knockdown of TRIM15 caused a significant increase in E-cadherin expression, as well as decreases in expression of N-cadherin and Vimentin proteins. Moreover, in vivo assay proved that tumor growth was suppressed by knockdown of TRIM15. Furthermore, the protein expression levels of β-catenin, C-myc, and CyclinD1 were markedly decreased in sh-TRIM15-infected ESCC cells. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM15 knockdown on ESCC cells. In conclusion, these findings indicated that knockdown of TRIM15 blocked the growth and metastasis of ESCC in part through inhibiting the Wnt/β-catenin signaling pathway. Thus, TRIM15 might serve as a promising therapeutic target for ESCC.

Keywords: Epithelial‐mesenchymal transition (EMT); Esophageal squamous cell carcinoma (ESCC); Metastasis; TRIM15; Wnt/β-catenin pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • DNA-Binding Proteins / metabolism*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Wnt Signaling Pathway*

Substances

  • DNA-Binding Proteins
  • tripartite motif-containing protein 15, human