Biological effect of ETV4 and the underlying mechanism of its regulatory effect on epithelial‑mesenchymal transition in intrahepatic cholangiocarcinoma cells.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a highly invasive malignant tumor. The prognosis of patients with ICC after radical surgical resection remains poor, due to local infiltration, distant metastasis, a high recurrence rate and lack of effective treatment strategies. E26 transformation-specific sequence variant 4 (ETV4) is a pro-carcinogenic factor that is upregulated in several tumors; however, the role of ETV4 in ICC is relatively unknown. The present study aimed to determine the role of ETV4 in the Hccc9810 ICC cell line and to assess how it contributes to epithelial-mesenchymal transition (EMT) in ICC. Hccc9810 cells were infected with lentiviruses to construct stable ETV4-overexpressing cells, stable ETV4 knockdown cells and corresponding control groups. The Cell Counting Kit-8 and Transwell assays were used to quantify cell proliferation, invasion and migration, and the effects on cell cycle progression and apoptosis were detected by flow cytometry. ETV4 was identified as a driver of cell growth, invasion, migration and cell cycle progression, while restraining apoptosis in Hccc9810 cells. Reverse transcription-quantitative PCR and western blotting revealed that increased ETV4 levels may drive EMT by triggering the TGF-β1/Smad signaling pathway. This cascade, in turn, may foster tumor cell proliferation, migration, invasion and cell cycle advancement, and hinder apoptosis.