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

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

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作者:Hitesh Bhagavanbhai Mangukiya, Hema Negi, Siva Bharath Merugu, Qudsia Sehar, Dhahiri Saidi Mashausi, Fakhar-Un-Nisa Yunus, Zhenghua Wu, Dawei Li

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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