摘要
目的:研究C-X-C型趋化因子受体4(CXCR4)-整合素αVβ3(integrinαVβ3)介导头颈部鳞癌细胞迁移的分子生物学机制。方法:应用头颈部鳞癌细胞株HN-5,采用慢病毒转染方法构建CXCR4过表达的细胞株,用荧光显微镜观察基因表达情况;采用脂质体法将CXCR4-siRNA、integrinαVβ3-siRNA分别转染至HN-5细胞和CXCR4过表达的HN-5细胞中,Transwell小室实验检测HN-5细胞迁移能力,Western blot实验检测CXCR4、integrinαVβ3、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)和黏附斑激酶(FAK)-非受体型酪氨酸蛋白激酶(SRC)-细胞外信号调节激酶(ERK)信号通路相关蛋白的表达情况。结果:CXCR4过表达可上调HN-5细胞中integrinαVβ3表达水平,而抑制CXCR4表达可下调integrinαVβ3表达;CXCR4过表达可调控MMP-2和MMP-9促进癌细胞迁移,并激活FAK-SRC-ERK信号通路;而抑制integrinαVβ3表达可明显逆转CXCR4过表达对HN-5细胞的上述作用。结论:CXCR4过表达可通过integrinαVβ3促进头颈部鳞癌细胞迁移,其作用机制可能与激活FAK-SRC-ERK通路有关。
Objective:To study the molecular mechanism of CXCR4-integrinαVβ3 mediating migration of head and neck squamous cell carcinoma cells.Methods:Head and neck squamous cell carcinoma cell line HN-5 was used to construct CXCR4 overexpression cell line by lentivirus transfection,and the gene expression was observed by fluorescence microscope.CXCR4-siRNA and integrinαVβ3-siRNA were transfected into HN-5 cells and CXCR4-overexpressed HN-5 cells by liposome method,respectively.The migration ability of HN-5 cells was detected by Transwell chamber assay.The expressions of CXCR4,integrinαVβ3,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and adhesion spot kinase(FAK)-non-receptor tyrosine protein kinase(SRC)-extracellular signal-regulated kinase(ERK)signaling pathway related proteins were detected by Western blot analysis.Results:Overexpression of CXCR4 up-regulated the expression of integrinαVβ3 in HN-5 cells,while inhibition of CXCR4 down-regulated the expression of integrinαVβ3.CXCR4 overexpression can regulate MMP-2 and MMP-9 to promote cancer cell migration and activate FAK-SRC-ERK signaling pathway.Inhibition of integrinαVβ3 expression significantly reversed the above effects of CXCR4 overexpression on HN-5 cells.Conclusion:CXCR4 overexpression can promote the migration of head and neck squamous cell carcinoma cells through integrinαVβ3,and its mechanism may be related to the activation of FAK-SRC-ERK pathway.
作者
常艳艳
李鹏
孟金平
陈艳艳
CHANG Yanyan;LI Peng;MENG Jinping;CHEN Yanyan(Department of Head and Neck Thyroid,Henan Cancer Hospital,Henan Zhengzhou 450000,China)
出处
《现代肿瘤医学》
CAS
北大核心
2023年第9期1584-1588,共5页
Journal of Modern Oncology
基金
河南省医学科技攻关计划项目(编号:2018020488)。
