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

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Adhesion & Migration Pub Date : 2019-01-01 DOI:10.1080/19336918.2019.1685928

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

摘要

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。

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

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.

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来源期刊

Cell Adhesion & Migration CELL BIOLOGY-

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

53 weeks

期刊介绍： Cell Adhesion & Migration is a multi-disciplinary, peer reviewed open access journal that focuses on the biological or pathological implications of cell-cell and cell-microenvironment interactions. The main focus of this journal is fundamental science. The journal strives to serve a broad readership by regularly publishing review articles covering specific disciplines within the field, and by publishing focused issues that provide an overview on specific topics of interest within the field. Cell Adhesion & Migration publishes relevant and timely original research, as well as authoritative overviews, commentaries, and perspectives, providing context for the work presented in Cell Adhesion & Migration and for key results published elsewhere. Original research papers may cover all topics important in the field of cell-cell and cell-matrix interactions. Cell Adhesion & Migration also publishes articles related to cell biomechanics, biomaterial, and development of related imaging technologies.