FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1.
FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1.
复制标题
FGF7/FGFR2信号通过上调血小板反应蛋白-1促进人胃癌的侵袭和迁移
DOI：
10.3892/ijo.2017.3927
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发表时间：
2017-05
影响因子：
5.2
通讯作者：
Qiu H
中科院分区：
文献类型：
--
作者：
Huang T;Wang L;Liu D;Li P;Xiong H;Zhuang L;Sun L;Yuan X;Qiu H
成纤维细胞生长因子7（FGF 7）是间充质特异性肝素结合生长因子，其结合FGF受体2（FGFR 2）以调节许多细胞和生理过程。FGF 7/FGFR 2信号与胃癌进展相关。在本研究中，我们研究了FGF 7/FGFR 2促进人胃癌侵袭和迁移的分子机制。我们首次证明人胃癌组织中FGFR 2表达的增加与人胃癌组织中的肿瘤深度和临床分期显著相关。凝血酶敏感蛋白1（Thrombospondin 1，THBS 1）是一种细胞外糖蛋白，在细胞-基质和细胞-细胞相互作用中发挥多种作用。THBS 1的表达与肿瘤分化程度密切相关。FGFR 2和THBS 1在胃癌组织中的表达均高于癌旁正常组织，且两者的表达呈正相关。在体外，FGF 7对细胞侵袭和迁移的刺激被FGFR 2敲低部分抑制。此外，FGF 7/FGFR 2上调THBS 1，通过敲低THBS 1降低细胞侵袭和迁移。此外，PI 3 K/Akt/mTOR信号通路主要负责FGF 7/FGFR 2诱导的THBS 1上调。综上所述，我们的数据表明，FGF 7/FGFR 2/THBS 1与人胃癌的侵袭和迁移的调节有关。
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.