TEAD4 promoted proliferation and metastasis of gallbladder cancer by regulation of TMPRSS4.

Abstract

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed at advanced stages. TEA domain transcription factor 4 (TEAD4) has been implicated in mediating the progression of various cancers, but its function and underlying mechanism in gallbladder cancer remain unclear. This study assessed the expression levels of TEAD4 and TMPRSS4 using reverse transcription quantitative polymerase chain reaction and western blotting. The functional role of TEAD4 in the progression of gallbladder cancer was investigated through CCK-8, EdU assays, Transwell, wound-healing assays, western blotting, immunohistochemistry, and hematoxylin and eosin (H&E) staining in cellular and animal models. The potential regulatory mechanism was explored by chromatin immunoprecipitation and dual-luciferase reporter assays. Results revealed that TEAD4 expression was significantly elevated in GBC tissues and cell lines. TEAD4 knockdown suppressed cell viability, decreased the percentage of EdU-positive cells, reduced invasive capacity, and increased wound closure width in GBC-SD and NOZ cells. Conversely, overexpression of TEAD4 produced opposite effects. Mechanistically, TEAD4 was predicted and confirmed to bind with the promoter region of TMPRSS4, as validated by the Chip-PCR and dual luciferase results. The mitigatory role of sh-TEAD4 on cell growth, invasion, and mobility of GBC was reversed by overexpression TMPRSS4 overexpression. In vivo, silencing of TEAD4 declined the tumor size and weight, the expression of TEAD4 and TMPRSS4, the ki-67 level, and the numbers of liver metastasis foci. In conclusion, the knockdown of TEAD4 suppressed the growth and metastasis of GBC via TMPRSS4.