Study On The Interaction Of T-cell Factor 4 And Wnt7b To Promote The Metastasis Of Gastric Cancer Cells

Background and Objectives Gastric cancer is one of the common malignant tumors.The number of new cases of gastric cancer in China each year is close to half of the global.Due to the lack of specific and simple detection indicators,most patients with gastric cancer find that they are in the middle and advanced stages at the time of consultation and lose the best opportunity for treatment.Therefore,there is an urgent need for a marker molecule that can be used for rapid diagnosis of gastric cancer in the clinic.The Wnt / ?-catenin pathway is a classic pathway in Wnt signaling and plays a key role in embryonic development and adult stem cell renewal and proliferation.Its abnormal activation of signals is thought to promote tumorigenesis and development.We have previously found that overexpression of the nuclear transcription factor T cytokine 4(TCF4,also known as TCF7L2)in the Wnt / ?-catenin pathway can promote gastric cancer cell proliferation and chemotherapy resistance,but the mechanism of action is unknown.This study revealed the mechanism by which TCF7L2 interacts with the downstream target gene Wnt7 b to promote gastric cancer cell metastasis,providing a basis for finding marker molecules for the diagnosis and treatment of gastric cancer and developing new drugs.Materials and Methods The expression of TCF7L2,Wnt7 b and other Wnt genes in gastric cancer cell lines and clinical samples were detected by PCR array and q PCR.NCI-N87 cells were treated with recombinant human Wnt7 b protein,TCF7L2 expression in gastric cancer cell line NCI-N87 was detected by q PCR and Western blot.?-Catenin / TCF binding activity of NCI-N87 cells was detected by double luciferase reporter gene detection system.Actinomycin D was used to analyze the effect of Wnt7 b on the stability of TCF7L2 m RNA,and Wound healing and Transwell experiments were used to analyze the effect of Wnt7 b on the migration ability of gastric cancer cells.Results By comparing the PCR array data between SGC7901 and SGC7901 / TCF7L2 and between NCI-N87 and NCI-N87 / sh TCF7L2 cell lines,Wnt7 b was the most significant Wnt ligand regulated by TCF7L2.The transcription levels of TCF7L2 and Wnt7 b in gastric cancer tissues was higher than those in matched normal tissues(P < 0.05).When NCI-N87 cells were treated with recombinant human Wnt7 b protein for 48 hours,TCF7L2 transcription level was significantly increased(P < 0.05),TCF7L2 mRNA stability was enhanced(P < 0.05),TCF7L2 protein level was increased(P < 0.05),and ?-Catenin / TCF binding activity was enhanced(P < 0.05),which suggested that Wnt7 b can improve Wnt / ?-catenin signaling pathway activity of NCI-N87 cells.Moreover,tt was also found that Wnt7 b could enhance the migration ability of NCI-N87 cells(P <0.05).Conclusion The experimental research in this paper shows that TCF7L2 and Wnt7 b in gastric cancer tissues are higher than normal tissues,and Wnt7 b and TCF7L2 promote the metastasis of gastric cancer cells through interaction.The results suggest that TCF7L2 and Wnt7b may become new molecular markers of gastric cancer or targets for drug intervention,which need further clinical research.