Matrix metalloproteinase-2 inducing COL1A1 synthesis via integrin alpha Ⅴ promotes invasion and metastasis of cholangiocarcinoma cells

作者：Shuguang Pan, Ying Hu, Lang Gan, Jiejuan Lai, Ping Zheng, Yujun Zhang, Ling Shuai, Yan Jiang, Mo Chen, Junping Wang, Yu He · 发表于：Annals of Hepatology · 年份：2023 · DOI：10.1016/j.aohep.2023.101279 · 被引用次数：12 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Cell Adhesion Molecules Research、Protease and Inhibitor Mechanisms

INTRODUCTION AND OBJECTIVES: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA. MATERIALS AND METHODS: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments. RESULTS: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was posi...