The Molecular Mechanism Of Tumor Microenvironment Regulating EMT-Mediated Invasion And Metastasis Of Head And Neck Cancer

Objectives: To study the specific molecular mechanism of tumor microenvironment regulating the invasion and metastasis of head and neck cancer,and to explore the new strategy of targeted therapy for metastatic head and neck cancer.Materials and methods: 1.The relationship between EMT-related genes and the invasion and metastasis of head and neck cancer was analyzed by Oncomine,TCGA database and gene chip.2.The expression of EMT-related proteins in head and neck cancer cells and head and neck cancer tissues was detected by Western blotting and immunohistochemistry.The relationship between EMT-related proteins and prognosis was also analyzed.3.The effect of EMT on the invasion and metastasis of head and neck cancer was studied by using cell transfection technique to establish high expression and knockout stable cell lines.4.The specific molecular mechanism of EMT in tumor microenvironment was studied by CHIP and immunoprecipitation.5.The animal model of lung metastasis of tail vein in nude mice was studied.The relationship between EMT and metastasis of head and neck cancer was studied experimentally.Results:1.The down-regulation of E-cadherin expression in EMT marker is closely related to the invasion and metastasis of head and neck cancer patients.2.The expression of TGF-β in the tumor microenvironment can induce the down-regulation of E-cadherin by induction of G9a-Snail complex into E-cadherin gene promoter region,induce EMT and promote lymph node metastasis of head and neck squamous cell carcinoma.3.Metastatic head and neck squamous cell carcinoma knockout G9 a can significantly inhibit its metastasis and stem cell characteristics.4.The expression of EMT-related protein Vimentin in metastatic head and neck cancer is an important index of metastasis and prognosis of head and neck squamous cell carcinoma.5.Metastatic adenoid cystic carcinoma through autocrine EREG,activation of EGFR signaling pathway,and thus stabilize the expression of Snail and Slug,promote adenoid cystic carcinoma of lung metastasis.6.Targeted EREG-EGFR-Snail/Slug signal axis can significantly inhibit the in vitro metastasis of adenoid cystic carcinoma and the pulmonary metastasis of tail vein injection in nude mice.Conclusions: 1.EMT was closely related to the invasion and metastasis of head and neck cancer patients.2.TGF-β and EREG can regulate the invasion and metastasis of head and neck cancer through EMT.3.EMT-related protein Vimentin is an important indicator of metastasis and prognosis of head and neck squamous cell carcinoma.4.G9a-Snail signal axis-mediated down-regulation of E-cadherin expression is an important molecular mechanism of invasion and metastasis of head and neck cancer,and can be used as a potential target for the treatment of head and neck squamous cell carcinoma.5.EREG-EGFR-Snail/Slug signal axis is an important molecular mechanism of lung metastasis of adenoid cystic carcinoma and can be used as a potential target for the treatment of metastatic adenoid cystic carcinoma.