The Role Of Integrin αvβ6-ERK In The Progression Of Colon Cancer

Background:A family of cell membrane glycoproteins that are heterodimers composed of α-and β-chain subunits. They serve as extracellular matrix glycoprotein receptors involved in cell adhesion for example the mediation of adhesion of neutrophils to endothelial cells. Integrin are receptors that mediate the attachment between a cell and the tissues that surround it, such as other cells or the extracellular matrix (ECM). In signal transduction, integrins pass information about the chemical composition of the ECM into the cell. Therefore, they are involved in cell signaling and the regulation of cell cycle, shape, and motility. Integrin are expressed on endothelial cells, leukocytes, other cells and platelets. They act as receptors for fibrinogen.Integrins work alongside other receptors such as cadherins, the immunoglobulin superfamily cell adhesion. This study aims to further clarify the Integrin avP6 between cadherin Fat1 and regulation of the expression and signal transduction pathways that may be involved, and further revealing the molecular mechanism of malignant invasion of colon.Objective:The aim of this study is to detect whether the integrin αpβ6 can regulate cadherin Fat-1 in colon cancer or not, and the signal pathway, further to disclose the molecular mechanism of colon cancer cell invasion.Material & Methods:We culture HT-29 and SW480 colon cancer cell lines, respectively. SiRNA and transgenes technology were used to choose HT-29 and SW480 colon cancer cell groups. Western Blotting was used to detect the Total-ERK, phosphate-ERK and Fat-1 protein level in colon cancer. After colon cancer cell were treated by PD98059, the special inhibitor of ERK, observing the expression of Fat-1 using western blotting. Zymorgraphy analysis was used to detect the Gelatinase B, which was secreted by colon cancer in gel.Results:Via interrupting the expression of Integrin<xvp6 can negatively regulate the expression of Fat-1, and inhibit the phosphorylation of ERK by PD98059 can block the αvβ6 inhibition on Fat-1. Zymorgraphy analysis shown that integrin avP6 can increase the level of Gelatinase B.Conclusion:Integrin αvβ6 can negatively regulate the expression of Fat-1, and the αvβ6-ERK signaling pathway may be participated in the molecular mechanism, strengthen the expression of αvβ6 can promote the colon cancer cell invasion.