Galectin-1 from cancer-associated fibroblasts induces epithelial–mesenchymal transition through β1 integrin-mediated upregulation of Gli1 in gastric cancer

作者：Yang Chong, Dong Tang, Qingquan Xiong, Xuetong Jiang, Chuanqi Xu, Yuqin Huang, Jie Wang, Huaicheng Zhou, Youquan Shi, Xiaoqing Wu, Daorong Wang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2016 · DOI：10.1186/s13046-016-0449-1 · 被引用次数：70 · 研究领域：Galectins and Cancer Biology、Glycosylation and Glycoproteins Research、Wnt/β-catenin signaling in development and cancer

BACKGROUND: Gastric cancer (GC) is characterized by the excessive deposition of extracellular matrix, which is thought to contribute to this tumor's malignant behavior. Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Galectin-1 (Gal-1), a β-galactoside-binding protein abundantly expressed in activated cancer-associated fibroblasts (CAFs), has been reported to be involved in GC progression and metastasis by binding to β1 integrin, which, in turn, can bind to matrix proteins and activate intracellular cascades that mediate EMT. Increasing evidence suggests that abnormal activation of the hedgehog (Hh) signaling pathway enhances GC cell migration and invasion. The purpose of our study is to explore the role of Gal-1 in the GC progression and metastasis as well as the regulatory mechanism. METHODS: We hypothesized that Gal-1 binding to β1 integrin would lead to paracrine signaling between CAFs and GC cells, mediating EMT by upregulating Gli1. Invasion and metastasis effects of the Gal-1 and Gli1 were evaluated using wound healing and invasion assay following transfection with mimics. Additionally, to facilitate the delineation of the role of the Hh signaling in GC, we monitored the expression level of associated proteins. We also evaluated the effects of β1 integrin on these processes. Furthermore, Gal-1 and Gli1 expression in GC patient samples were examined by immunohistochemistry and western blot to determine the corr...