The Mechanism Ofaction And Function Of VWCE In Breast Cancer Metastasis

Objective:Breast cancer is the highest rate of female morbidity and mortality in the world.Von Willebrand factor C and EGF structural domain proteins(VWCE)are members of the EGF family and play an important role in hepatocellular carcinoma and gastric cancer,but their role,regulatory mechanism and clinical value in breast cancer are not yet clear.In this paper,QPCR experiment was used to detect the mRNA level of VWCE in breast cancer patients,and the expression of VWCE in breast cancer tissue was found to be reduced,but the function of VWCE in breast cancer has not been studied.The purpose of this study was to discuss the biological characteristics and regulatory mechanisms of VWCE in breast cancer.Method: 1.hrough the VWCE of breast cancer cells to dye the slow virus to stabilize the expression of VWCE;2.QPCR experiment,Western blot experiment to detect the expression of VWCE mRNA and protein in breast cancer;3.CCK8,plate cloning experiment,nude mouse subcutaneous tumor test to detect whether VWCE affects the proliferation of breast cancer cells outside the body;4.Scratch experiment,Transwell experiment,and the construction of nude rat lung metastasis model to detect the effect of VWCE on the invasion and metastasis ofbreast cancer;5.flow cytometry to detect the effect of VWCE on breast cancer cycle and apoptosis;6.iTRAQ proteomics experiment to detect the possible role of VWCE protein;7.immunohistochemical experiment to detect the expression of VWCE in breast cancer patients,EMT related markers in lung metastasis tissue expression.Results: Through the above experimental methods,we found that:(1)VWCE was significantly reduced in the tissues and cell lines of breast cancer.(2)The expression of VWCE in breast cancer cells could inhibit the proliferation and of breast cancer cells.(3)the expression of VWCE in breast cancer cells could inhibit the invasion and metastasis of breast cancer cells.(4)VWCE expression can induce invasive breast cancer cell EMT inversion into MET.(5)VWCE expression leads to the stagnation of breast cancer cell cycle in the G1 period,inhibiting the resistance of breast cancer cells.(6)WDR1 expression reverses the inhibitory effect of VWCE in breast cancer cells.(7)The expression of VWCE and WDR1 is obviously related to the survival of breast cancer,the higher the expression of VWCE,the longer the survival period of breast cancer patients.And the lower the expression of WDR1,the longer the patient's survival period.Conclusion: the reduction of VWCE in breast cancer regulates the expression of WDR1 and promotes the progression of breast cancer.It is indicated that VWCE may be a new type of tumor inhibitor,which mainly inhibits the development of breast cancer by lowering WDR1.