MYC下调人整合素分子β1抑制卵巢癌细胞黏附侵袭能力

MYC suppresses ovarian cancer cell adhesion and invasion ability through downregulation of human integrin β1

目的:探讨MYC对卵巢癌细胞黏附侵袭能力的影响,以及整合素分子β1(ITGB1)参与调控的机制。方法:比较NCI-60细胞信息库中60种细胞系MYC与ITGB1的mRNA水平的相关性;Western blot比较卵巢癌细胞系中MYC与ITGB1蛋白水平的相关性;免疫组化比较配对卵巢癌原位转移灶MYC和ITGB1表达水平;体外黏附试验比较改变MYC或ITGB1水平后卵巢癌细胞对不同ECM蛋白如Fibronectin、CollagenⅠ、Laminin的黏附能力;Transwell试验比较改变MYC或ITGB1水平后卵巢癌细胞的侵袭能力。结果 :NCI-60细胞库中MYC与ITGB1在mRNA水平显著负相关(P<0.01);卵巢癌细胞系中MYC和ITGB1蛋白水平负相关;卵巢癌配对临床标本原位灶低表达ITGB1,高表达MYC,而转移灶高表达ITGB1低表达MYC;下调ITGB1降低卵巢癌细胞黏附和侵袭能力,过表达ITGB1则促进黏附和侵袭能力;下调MYC后上调ITGB1表达,促进黏附和侵袭能力,抑制ITGB1的升高可以逆转黏附和侵袭能力的提高。结论:卵巢癌细胞中MYC与ITGB1负相关,抑制卵巢癌细胞黏附与侵袭,下调MYC可以通过升高ITGB1促进其侵袭和黏附能力。

Objective To explore the influence of MYC expression level on ovarian cancer cells adhesion and invasion ability, and the involvement of the integrin β1 in the adhesion and invasion control. Methods Comparative study was done to analyze the relationship between the mRNA level of MYC and ITGB1 among sixty cell lines from the NCI-60 cells bank; Western blot was performed to demonstrate the correlation of MYC and ITGB1 protein level in ovarian cancer cell lines; Immunohistochemistry was adopted to compare the expression level of MYC and ITGB1 in paired primary and metastatic ovarian cancer tissue. Furthermore, we employed in vitro adhesion test to detect the alteration of ovarian cancer cell adhesion ability to ECM molecular like fibronectin, collagen I and laminin after fluctuation of MYC and ITGB1 expression; Transwell assay was applied to check the invasion ability variation with the disturbance of MYC and ITGB1 level. Results The mRNA levels of MYC and ITGB1 were dramatically inverse-correlated in NCI-60 cells bank（P〈0.01） ;The protein levels of MYC and ITGB1 in ovarian cancer cell lines were also negative correlated; The primary ovarian cancer tissue showed lower expression of ITGB1 and higher expression of MYC, while the matched metastasis displayed the opposite outcome;Ovarian cancer cells reduced adhesive and invasive capacity in case of ITGB 1 being down-regulated, however, the adhesive and metastatic ability improved tremendously with elevation of ITGBl;Promoted adhesion and invasion ability and rise of ITGB1 expression were observed after downregulation of MYC,meanwhile,and inhibition of ITGB1 reversed the increasement of adhesion and invasion ability. Conclusions MYC, inversely-correlated with ITGB1 in ovarian cancer cells, inhibited ovarian cancer ceils adhesion and invasion. Inhibition of MYC could lead to enhanced adhesion and invasion ability of ovarian cancer cells.