Epithelial–mesenchymal transition with expression of SNAI1-induced chemoresistance in colorectal cancer

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• 作者：Hiromitsu Hoshino ; Norikatsu Miyoshi ; Ken-ichi Nagai ; Yoshito Tomimaru ; Hiroaki Nagano ; Mitsugu Sekimoto ; Yuichiro Doki ; Masaki Mori ; Hideshi Ishii
• 关键词：SNAI1 ; Epithelial– ; mesenchymal transition ; Chemoresistance ; Colorectal cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：18 December 2009
• 年：2009
• 卷：390
• 期：3
• 页码：1061-1065
• 全文大小：394 K

文摘

Background

Previous reports have demonstrated that SNAI1 plays a role in epithelial–mesenchymal transition (EMT) through the suppression of CDH1. Its role in the pathology and regulation of EMT expression to chemoresistance in colorectal cancer (CRC) has not yet been fully elucidated.

Methods

Immunohistochemistry was performed to evaluate the expression of Snai1 protein in 30 primary CRC samples. The biological significance of Snai1 expression was studied by induction of the wild-type (WT) and mutant SNAI1 gene in CRC SW480 cells.

Results

Examination of 20 surgical specimens of CRC indicated that Snai1 protein expression was localized outer regions of invasive tumors. Introduction of phosphorylation-defective active EMT forms, SNAI1-6SA and SNAI1-8SA, caused downregulation of CDH1 and upregulation of VIM compared with SNAI1-WT and the negative control (NC). Chemoresistance to 5-fluorouracil (IC50) was higher in SNAI1-6SA and SNAI1-8SA transfectants compared with SNAI1-WT and NC. All the above results were significantly different.

Conclusion

The present study demonstrated that Snai1 plays a role in CRC invasion through phosphorylation, suggesting a plausible mechanism for overcoming chemoresistance that will lead to the development of effective treatments for CRC.