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

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.

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