Human Epidermal Growth Factor Receptor 2 Interacts With β-catenin / TCF7L2 Signaling To Promote Ovarian Cancer Cell Metastasis

Background and ObjectivesOvarian cancer in gynecologic cancer mortality ranked first,the early lack of specific symptoms,when the obvious symptoms or metastases of the primary tumor,the majority of cases were found.About two-thirds of high-grade ovarian cancer patients have malignant progression,causing tumor recurrence and chemoresistance.Abnormal activation of Wnt / β-catenin signaling pathway and EGFR signaling pathway is closely related to the occurrence and development of various tumors.HER2 plays a central role in the EGFR family.TCF7L2 and β-catenin are two key nodes of wnt signaling pathway molecular.The study found that in the process of tumor progression,HER2 andβ-catenin / TCF7L2 signal interaction.In this thesis,we investigated the interaction between human epidermal growth factor receptor 2(HER2)and β-catenin / TCF7L2 signaling in ovarian cancer cells and their effects on ovarian cancer cell metastasis.Materials and MethodsThe expression of HER2 and T-cell factor 4(TCF4)in ovarian cancer cell line SKOV3 was detected by Western blotting.SKOV3 cell line with HER2 or TCF4 knockdown was constructed by lentiviral vector and named as SKOV3-shHER2 and SKOV3-shTCF4 cells.Transwell and cell scratch assay were used to compare the effects of different gene expression levels on the migration ability of SKOV3 cells.By using receptor antagonist EGF and wnt3 a,and iCRT14,a small molecule inhibitor targeting TCF4 / β-catenin,Its effect on the expression of HER2,β-catenin and TCF4 and the cell migration ability of cells.ResultsOvarian cancer cell line SKOV3 overexpresses HER2 and TCF4.Knockdown the expression of HER2,the protein level of β-catenin and TCF4 decreased(P <0.05);knockdown of TCF4 expression also decreased the protein level of HER2(P <0.05);and the cell migration ability was significantly decreased <0.05).After treated with EGF for 0-12 hours,the expression of HER2 in SKOV3 cells increased with the stimulation time,and the expression of β-catenin and TCF4 also increased(P <0.05).Wnt3 a treatment with 0-24 After hours,the expression of β-catenin and TCF4 increased with the prolongation of stimulation time and the expression of HER2 also increased(P<0.05).After treated with iCRT14,a specific inhibitor of TCF4 / β-catenin,for 0-12 hours The expression of β-catenin and TCF4 decreased with the prolongation of treatment time and the expression of HER2 also decreased(P <0.05).The migration ability of SKOV3-shHER2 or SKOV3-shTCF4 cells was significantly increased after EGF and wnt3 a treatment for 12 hours(P <0.05).Cell migration ability of SKOV3 cells treated with iCRT14,a specific inhibitor of TCF4 / β-catenin,was significantly decreased(P <0.05).ConclusionIn this paper,our experimental studies have shown that ovarian cancer cells HER2 receptor signaling and β-catenin / TCF7L2 signal transduction pathway interaction,can play a role in promoting ovarian cancer cell metastasis.The results suggest that molecules such as HER2,β-catenin and TCF7L2 may be the new molecular targets of ovarian cancer or drug intervention,pending further clinical study.