Open AccessBlocking FGFR4 exerts distinct anti‐tumorigenic effects in esophageal squamous cell carcinoma
Author(s) -
Xin Zhongwei,
Song Xuemin,
Jiang Bin,
Gongsun Xin,
Song Liang,
Qin Qiming,
Wang Qiang,
Shi Mo,
Liu Xiangyan
Publication year - 2018
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12883
Subject(s) - cancer research , medicine , fibroblast growth factor receptor 4 , mapk/erk pathway , cell growth , apoptosis , epithelial–mesenchymal transition , angiogenesis , pi3k/akt/mtor pathway , cancer , protein kinase b , cell , fibroblast growth factor , biology , fibroblast growth factor receptor , signal transduction , receptor , metastasis , microbiology and biotechnology , biochemistry , genetics
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.