FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1.
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.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Tingting
T
Huang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Lei
L
Wang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Dian
D
Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Piao
P
Li
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Huihua
H
Xiong
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Liang
L
Zhuang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Li
L
Sun
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Xianglin
X
Yuan
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Hong
H
Qiu
D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
C496453:FGF7 protein, human; D019700:Thrombospondin 1; C000611726:thrombospondin-1, human; D051523:Fibroblast Growth Factor 7; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2