标题：Blocking FGFR4 exerts distinct anti-tumorigenic effects in esophageal squamous cell carcinoma
作者：Xin, Zhongwei; Song, Xuemin; Jiang, Bin; Xin Gongsun; Song, Liang; Qin, Qiming; Wang, Qiang; Shi, Mo; Liu, Xiangyan
作者机构：[Xin, Zhongwei; Song, Xuemin; Jiang, Bin; Xin Gongsun; Song, Liang; Qin, Qiming; Wang, Qiang; Shi, Mo; Liu, Xiangyan] Shandong Univ, Dept Thorac Surg, 更多
通讯作者地址：[Liu, XY]Shandong Univ, Dept Thorac Surg, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.
关键词：Epithelial-mesenchymal transition (EMT); esophageal squamous cell; carcinoma (ESCC); FGFR4; H3B-6527; proliferation
摘要：Background The FGFR family can be activated by FGFs and plays important roles in regulating cell growth, differentiation, migration, and angiogenesis. Recent studies have suggested that FGFR4 could regulate several processes, including tumor progression. Esophageal squamous cell carcinoma (ESCC) is a malignancy with high global occurrence. However, the molecule mechanism and the potential roles of FGFR4 in ESCC remain unknown.; Methods Immunohistochemistry and Western blotting were used to detect FGFR4 expression in ESCC samples and cell lines. Cell counting kit-8, and clonogenic, transwell, flow cytometric, and tumor xenograft in nude mice assays were utilized to determine the effect of blocking FGFR4 in proliferation, invasion, migration, and apoptosis of ESCC cells.; Results FGFR4 is frequently overexpressed in ESCC tissue and cell lines. in vitro assays have shown that blocking FGFR4 by a specific blocker, H3B-6527, significantly decreases proliferation, invasion, and migration, and alters epithelial-mesenchymal transition markers in ESCC cells. In addition, FGFR4 blockade is associated with the induction of apoptosis and affects PI3K/Akt and MAPK/ERK pathways. Moreover, FGFR4 blockade could significantly inhibit the growth of xenograft tumors in vivo.; Conclusion Our findings suggest that blocking FGFR4 significantly suppresses the malignant behaviors of ESCC and indicate that FGFR4 is a potential target for the treatment of ESCC.