TY - JOUR
T1 - Epithelial-mesenchymal transition with expression of SNAI1-induced chemoresistance in colorectal cancer
AU - Hoshino, Hiromitsu
AU - Miyoshi, Norikatsu
AU - Nagai, Ken ichi
AU - Tomimaru, Yoshito
AU - Nagano, Hiroaki
AU - Sekimoto, Mitsugu
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
PY - 2009/12/18
Y1 - 2009/12/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70449697859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449697859&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.10.117
DO - 10.1016/j.bbrc.2009.10.117
M3 - Article
C2 - 19861116
AN - SCOPUS:70449697859
SN - 0006-291X
VL - 390
SP - 1061
EP - 1065
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
