The role of integrin ανβ6 in regulation of extracellular matrix degradation of colon cancer cells / 中华老年医学杂志

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.