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2016 ; 107
(5
): 619-28
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SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic
implantation model of colorectal cancer
#MMPMID26892864
Matsuda Y
; Miura K
; Yamane J
; Shima H
; Fujibuchi W
; Ishida K
; Fujishima F
; Ohnuma S
; Sasaki H
; Nagao M
; Tanaka N
; Satoh K
; Naitoh T
; Unno M
Cancer Sci
2016[May]; 107
(5
): 619-28
PMID26892864
show ga
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-? 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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