Journal Article SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer

Matsuda, Yasufumi  ,  Miura, Koh  ,  Yamane, Junko  ,  Shima, Hiroshi  ,  Fujibuchi, Wataru  ,  Ishida, Kazuyuki  ,  Fujishima, Fumiyoshi  ,  Ohnuma, Shinobu  ,  Sasaki, Hiroyuki  ,  Nagao, Munenori  ,  Tanaka, Naoki  ,  Satoh, Kennichi  ,  Naitoh, Takeshi  ,  Unno, Michiaki

107 ( 5 )  , pp.619 - 628 , 2016-05 , John Wiley & Sons Australia, Ltd
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 of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. 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, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-β signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well.

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