Serum response factor enhances liver metastasis of colorectal carcinoma via alteration of the E-cadherin/beta-catenin complex.
Serum response factor (SRF) is a transcription factor that controls cell growth, differentiation, and tumor progression as well as muscle development and function. Reduced expression of cell adhesion molecules has been reported to be associated with tumor metastasis. The aim of this study was to evaluate the expression and a role of SRF in liver metastasis of primary colorectal carcinomas. We examined the expression of SRF, E-cadherin, and beta-catenin by the use of immunochemical staining in 43 cases as a set of primary colorectal carcinomas and liver metastases. We also examined the role of SRF in colorectal carcinoma by overexpression of SRF in a colon cancer cell line. In metastatic carcinoma surgical samples, there was a marked increased expression of SRF as compared to expression in primary colorectal carcinoma surgical samples (P<0.05). E-cadherin expression was significantly decreased in metastatic liver carcinoma samples as compared to primary colorectal carcinoma samples (P<0.001). Frequent nuclear translocation of beta-catenin protein in primary and metastatic carcinoma cells was observed. Overexpression of SRF in SW480 cells resulted in a decreased expression of E-cadherin and an increased expression of non-phosphorylated nuclear beta-catenin. Overexpression of SRF in colorectal carcinoma cells enhanced cell motility and invasiveness. These results indicate that overexpression of SRF in colorectal carcinoma cells is associated with modulation of E-cadherin/beta-catenin expression and may play an important role in colorectal cancer metastasis.
Choi
Ha Na
HN
Department of Pathology, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonbuk 561-756, Korea.
Kim
Kyung Ryoul
KR
Lee
Ji Hyun
JH
Park
Ho Sung
HS
Jang
Kyu Yun
KY
Chung
Myoung Ja
MJ
Hwang
Si Eun
SE
Yu
Hee Chul
HC
Moon
Woo Sung
WS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D026362:Serum Response Factor / Q000378:metabolism*; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015820:Cadherins; D026362:Serum Response Factor; D051176:beta Catenin