ETV5 overexpression contributes to tumor growth and progression of thyroid cancer through PIK3CA

Life Sci. 2020 Jul 15;253:117693. doi: 10.1016/j.lfs.2020.117693. Epub 2020 Apr 20.

Abstract

Aims: Thyroid cancer is a common endocrine malignancy and sex hormone plays an important role in it. We have previously shown that activation of estrogen receptor (ER) α promotes thyroid cancer cell proliferation and invasion. Here, we attempted to investigate the role of ETS variant 5 (ETV5) on estrogen drived thyroid malignancy.

Main methods: Ten patients with follicular thyroid cancer were enrolled in this study. Cell proliferation and migration ability were analyzed by CCK-8 assay and cell migration assay, respectively. Chromatin immunoprecipitation-PCR and luciferase assay were conducted to analyze the relationship of ETV5 and PIK3CA.

Key findings: ETV5 is highly expressed in thyroid tissues from patients with follicular thyroid cancer as well as in FTC133 cells. 17b-estradiol or overexpression of ERα induced an increase in ETV5 protein level in FTC133 cells. Knockdown of ETV5 inhibited FTC133 cell proliferation, migration, and epithelial-mesenchymal transition, while 17b-estradiol could not correct this effect. Additionally, the level of PIK3CA was markedly decreased in ETV5 knockdown cells and had a positive correlation with ETV5 in thyroid cancer patients. Chromatin immunoprecipitation-PCR analysis and luciferase assay confirmed that ETV5 directly targeted PIK3CA and that ETV5 was bound to the promoter region of PIK3CA. In addition, PIK3CA overexpression abrogated ETV5-induced cell growth, migration and epithelial-mesenchymal transition.

Significance: ETV5 enhanced cell proliferation, migration, and epithelial-mesenchymal transition through the PIK3CA signaling pathway, indicating that ETV5 may be a therapeutic target in thyroid cancer.

Keywords: ETS variant 5; Epithelial-mesenchymal transition; Estrogen receptor; PIK3CA; Thyroid cancer.

MeSH terms

  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / pathology*
  • Adult
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromatin Immunoprecipitation
  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Middle Aged
  • Signal Transduction
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • ETV5 protein, human
  • Estrogen Receptor alpha
  • Transcription Factors
  • estrogen receptor alpha, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human

Supplementary concepts

  • Thyroid cancer, follicular