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.

中文翻译：

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AGR2 的旁分泌信号刺激成纤维细胞中的 RhoA 功能并调节细胞伸长和迁移。

众所周知，肿瘤基质中最重要的癌症相关成纤维细胞（CAF）可形成保护性结构以支持肿瘤生长。前梯度 2 (AGR2) 是一种肿瘤分泌蛋白，被认为在肿瘤微环境 (TME) 发育过程中发挥着关键作用。在这里，我们报告细胞外 AGR2 显着增强成纤维细胞的伸长和迁移。RhoA 的早期刺激表明，通过成纤维细胞生长因子受体 (FGFR) 和血管内皮生长因子受体 (VEGFR) 上调 G1-S 期调节蛋白细胞周期蛋白 D1 和 FAK 磷酸化与 AGR2 相关。我们的发现表明，分泌型 AGR2 改变成纤维细胞的伸长、迁移和组织，表明分泌型 AGR2 作为潜在的分子靶点，可能负责改变成纤维细胞浸润以支持肿瘤生长。