Paracrine signalling of AGR2 stimulates RhoA function in fibroblasts and modulates cell elongation and migration

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
H. B. Mangukiya, H. Negi, S. B. Merugu, Qudsia Sehar, D. S. Mashausi, F. Yunus, Zhenghua Wu, Dawei Li
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引用次数: 4

Abstract

ABSTRACT 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.
AGR2的旁分泌信号传导刺激成纤维细胞中的RhoA功能并调节细胞延伸和迁移
肿瘤基质中最重要的癌症相关成纤维细胞(CAFs)形成一种支持肿瘤生长的保护性结构。前梯度-2 (AGR2)是一种肿瘤分泌蛋白,被认为在肿瘤微环境(TME)的发展中起着关键作用。在这里,我们报道细胞外AGR2显著增强成纤维细胞的延伸和迁移。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), G1-S阶段调节蛋白cyclin D1和FAK磷酸化上调与AGR2相关。我们的发现表明,分泌性AGR2改变成纤维细胞的延伸、迁移和组织,表明分泌性AGR2可能是一个潜在的分子靶点,可能负责改变成纤维细胞的浸润,以支持肿瘤生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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