Blocking FGFR4 exerts distinct anti‐tumorigenic effects in esophageal squamous cell carcinoma

Abstract

BackgroundThe 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.MethodsImmunohistochemistry 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.ResultsFGFR4 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.ConclusionOur 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.

Downregulation of long non‐coding RNA LOC101928477 correlates with tumor progression by regulating the epithelial‐mesenchymal transition in esophageal squamous cell carcinoma

“…EMT has been widely accepted as a critical factor in tumor initiation and metastasis 9,26,35,37 . Its key regulatory role in invasion and metastasis has been reported in many human cancers including ESCC 25,28,34,38,39 . EMT has also been connected to the induction of immunosuppression and drug resistance 27,40 .…”

“…GAPDH (1:5000, Proteintech) was used as control. The results were quantified by Quantity One software (Bio‐Rad) 11,26,29,34 …”

An updated meta-analysis of the association between fibroblast growth factor receptor 4 polymorphisms and susceptibility to cancer

“…Overexpression of FGFR4 predict metastasis and poor survival outcome in various cancers [ 56–58 ]. Blocking FGFR4 significantly suppresses the cancer and indicates that FGFR4 is a potential target for the cancer treatment [ 59 ]. Polymorphisms in the FGFR4 rs351855 (Gly 388 Arg) polymorphism, is positioned in the transmembrane domain of the EGFR4.…”

An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk

“…These experimental results make FGFR4 an interesting therapeutic target, the safety of which has already been proven in clinical trials in cardiovascular diseases (reported at www.clinicaltrials.gov : NCT02476019). In addition, FGFR4 blockade is currently used in oncology trials as neoadjuvant chemotherapy to improve patients’ response, since it has a beneficial anti-angiogenic effect ( Xin et al, 2018 ; Gluz et al, 2020 ).…”