School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Engineering Research center of Cell and Therapeutic Antibody of Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
Cell Adh Migr. 2019 Dec;13(1):332-344. doi: 10.1080/19336918.2019.1685928.
The most prominent cancer-associated fibroblasts (CAFs) in tumor stroma is known to form a protective structure to support tumor growth. Anterior gradient-2 (AGR2), a tumor secretory protein is believed to play a pivotal role during tumor microenvironment (TME) development. Here, we report that extracellular AGR2 enhances fibroblasts elongation and migration significantly. The early stimulation of RhoA showed the association of AGR2 by upregulation of G1-S phase-regulatory protein cyclin D1 and FAK phosphorylation through fibroblasts growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR). Our finding indicates that secretory AGR2 alters fibroblasts elongation, migration, and organization suggesting the secretory AGR2 as a potential molecular target that might be responsible to alter fibroblasts infiltration to support tumor growth.
肿瘤基质中最突出的癌症相关成纤维细胞（CAFs）被认为形成一种保护性结构，以支持肿瘤生长。已知肿瘤分泌蛋白前梯度-2（AGR2）在肿瘤微环境（TME）发展中起着关键作用。在这里，我们报告细胞外 AGR2 显著增强成纤维细胞的伸长和迁移。早期 RhoA 的刺激显示 AGR2 通过上调 G1-S 期调节蛋白细胞周期蛋白 D1 和 FAK 磷酸化与成纤维细胞生长因子受体（FGFR）和血管内皮生长因子受体（VEGFR）有关。我们的发现表明，分泌的 AGR2 改变了成纤维细胞的伸长、迁移和组织排列，表明分泌的 AGR2 可能是一个潜在的分子靶点，它可能负责改变成纤维细胞浸润以支持肿瘤生长。
