FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1

Abstract

Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer. We first demonstrated that increased FGFR2 expression in human gastric cancer tissues was significantly associated with tumor depth and clinical stage in human gastric cancer tissues. Thrombospondin 1 (THBS1) is an extracellular glycoprotein that plays multiple roles in cell-matrix and cell-cell interactions. Increased expression of THBS1 significantly correlated with tumor differentiation. FGFR2 and THBS1 expression were both increased in cancer tissues as compared with adjacent normal tissues and their expression was positively correlated. In vitro, FGF7 stimulation of cell invasion and migration was partially suppressed by the FGFR2 knockdown. In addition, FGF7/FGFR2 upregulated THBS1, and cell invasion and migration were decreased by knockdown of THBS1. Furthermore, the PI3K/Akt/mTOR signaling pathway was predominantly responsible for FGF7/FGFR2-induced THBS1 upregulation. Taken together, our data suggest that FGF7/FGFR2/THBS1 is associated with the regulation of invasion and migration in human gastric cancer.

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

“…1A) and was overexpressed in 44 cases (48.9%). As previously reported [16], FGFR2 was more strongly expressed in GC than in adjacent gastric tissue samples (Fig. 1B).…”

“…Associations between FGFR and TSP members have been previously reported by our group and others [15,16,28,29]. The production of TSPs is associated with FGFs and determines tumor invasion and metastasis.…”

“…As a follow-on from our previous study, which demonstrated that FGFR2 promotes GC cells invasion and migration by targeting TSPs in vitro [16], we undertook an evaluation of the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC.…”

“…Western blot was performed as previously described [16]. Briefly, whole-cell lysates were collected, and protein concentrations were quantified by a BCA Protein Assay Kit (AR0146, Boster Biological Technology Ltd, Wuhan, China).…”

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

“…Duquette et al (28) reported that ThbS1 high expression could promote ATC cell metastasis; however, THBS1 knockdown can decrease the levels of thrombospondin 1, integrin (ITG)α3, ITGα6 and ITGβ1 in the tumor microenvironment, thus inhibiting ATC cell migration. In other types of cancer, including breast cancer, gastric cancer and melanoma, it was demonstrated that the occurrence of LNM is significantly higher in THBS1-positive samples compared with THBS1-negative samples, which was meditated by the PI3K/Akt/mTOR signaling pathway and epithelial-to-mesenchymal transition (EMT) (29)(30)(31)(32). In the present study, THBS1 was also highly expressed and involved in cell adhesion and positive regulation of cell migration, according to the GO analysis.…”