SERPINI1 regulates epithelial–mesenchymal transition in an orthotopic implantation model of colorectal cancer

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摘要：

An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial–mesenchymal transition (EMT). In our study, in order to characterize the properties ofEMTin 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumorsin vivo, as well as cells culturedin vitro, were immunostained forEMTmarkers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E‐cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX‐1,COLO205, CloneA,HCT116, andSW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480,SW620, andCOLO320). We evaluated these findings in combination with microarray analyses, and selected five genes:CHST11,SERPINI1,AGR2,FBP1, andFOXA1. Next, we downregulated the expression ofSERPINI1with siRNAin the cells, the results of which showed reverse‐EMTchanges at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secretedSERPINI1 protein ofSW620 cells, which supported the importance ofSERPINI1 inEMT. The development of therapeutic strategies targetingEMTis ongoing, including methods targeting the transforming growth factor‐β signaling pathway as well as the Wnt pathway.SERPINI1 is an important regulator ofEMT. Our findings help to elucidate the signaling pathways ofEMT, hopefully clarifying therapeutic pathways as well.

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关键词：

Colorectal cancer epithelial–mesenchymal transition microarray analysis orthotopic implantation mouse model SERPINI1

DOI：

10.1111/cas.12909

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年份：

2016