The role of integrin ανβ6 in regulation of extracellular matrix degradation of colon cancer cells
10.3760/cma.j.issn.0254-9026.2010.12.011
- VernacularTitle:整合素ανβ6对结肠癌细胞胞外基质降解的调控作用
- Author:
Renhua ZHANG
;
Haiqing GAO
;
Xiaohui SUN
;
Jiayong WANG
;
Jun NIU
- Publication Type:Journal Article
- Keywords:
Colonic neoplasms;
Mitogen-activated protein kinases;
Integrin ανβ6;
RNA interference
- From:
Chinese Journal of Geriatrics
2010;29(12):1002-1006
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of integrin ανβ6 in the invasion of colon cancer cells and its molecular mechanisms for regulation of the extracellular matrix (ECM) degradation.Methods The RNA interfering technique was used to downregulate the expression of ανβ6 in colon cancer cells. The expression of ανβ6 in transfected cells was determined by RT-PCR and Western blot.The cell invasive capacity was evaluated by reconstituted basement membrane invasion assay. Western blot and gelatin zymography were used to determine whether the reduced αvβ6 expression affects extracellular signal-regulated kinase (ERK), P-ERK, urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) expressions. [3H]-labelled type Ⅳ collagen degradation assay was performed to asess if supression of integrin ανβ6 inhibits extracellular matrix degradation.Results Specific siRNA inhibited the expression of ανβ6 in both the protein and mRNA levels in HT29 cells. Down regulation of integrin ανβ6 inhibited ERK, P-ERK1/2 expressions, and the secretion of uPA. pro-MMP-9 and pro-MMP-2 in tumor conditioned medium. Supression of integrin ανβ6 inhibited MAPK dependent [3H]-labelled type Ⅳ collagen degradation. Conclusions These data in our study demonstrats that integrin ανβ6 plays important roles in the invasion of colon cancer cells. The ανβ6 regulates the secretion levels of uPA, pro-MMP-9, pro-MMP-2 and the ECM degradation through the MAPK pathway.
