KIF4A drives esophageal squamous cell carcinoma via Wnt/β-catenin signaling and predicts poor prognosis

Abstract

Esophageal squamous cell carcinoma (ESCC) accounts for >90% of esophageal cancer cases in China, with a 5-year overall survival rate of <30% for advanced disease. Kinesin family member 4A (KIF4A) is implicated in multiple malignancies; however, its functional mechanisms in ESCC remain incompletely elucidated. The present study investigated the prognostic value and tumor-promoting mechanism of KIF4A in ESCC. KIF4A expression was detected in 43 paired ESCC and adjacent non-malignant tissues, as well as in ESCC cell lines. Loss- and gain-of-function assays were performed to evaluate the effects of KIF4A on ESCC cell proliferation, migration and tumorigenesis in vitro and in vivo. RNA sequencing, co-immunoprecipitation and rescue experiments were conducted to explore its downstream regulatory pathway. The results revealed that KIF4A was significantly upregulated in ESCC tissues and cell lines, and its high expression was closely associated with advanced tumor stage and poor overall survival in patients with ESCC. KIF4A knockdown markedly inhibited ESCC cell proliferation, migration and in vivo xenograft tumor growth, whereas its overexpression exerted opposite oncogenic effects. Mechanistically, KIF4A exerted tumor-promoting effects by activating the canonical Wnt/β-catenin signaling pathway via stabilization of the β-catenin/T-cell factor 7 complex. In conclusion, KIF4A may drive ESCC progression by activating the Wnt/β-catenin signaling pathway, and may serve as a promising prognostic biomarker and therapeutic target for ESCC.