ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2

Int J Med Sci. 2022 Jun 21;19(6):1072-1081. doi: 10.7150/ijms.71892. eCollection 2022.

Abstract

Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.

Keywords: ETV5; Esophageal squamous cell carcinoma; MMPs; SKA1; TRPV2; metastasis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Transcription Factors / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • ETV5 protein, human
  • SKA1 protein, human
  • TRPV Cation Channels
  • TRPV2 protein, human
  • Transcription Factors