| Gastric cancer is one of the most common cancers in the world and one of the most common causes of cancer-related deaths worldwide.Globally,gastric cancer ranks fourth in cancer incidence,Gastric cancer is the second leading cause of cancer deaths.The majority of gastric cancer patients have reached advanced stage when diagnosed,losing the best time of surgery,or having a high recurrence rate after resection.For advanced stage patients,most have shown metastasis.local adjuvant or neoadjuvant therapy combined with surgery is usually associated with a poor prognosis.The median survival of patients is about 1 year.To find early diagnosis and effective targeted therapy is the focus of gastric cancer research in recent years.Trefoil factor family 3(TFF3)is a member of the trefoil factor family protein specifically expressed in the gastrointestinal tract.TFF3 is mainly secreted in intestinal mucosa and is not detected in gastric mucosa,but is expressed in gastric cancer.TFF3 is an oncogene,which is closely related to the development and progression of gastric cancer.The growth,apoptosis and migration of gastric cancer cells are regulated by NF-κB,EGFR and PI3K-Akt pathways.TFF3 can promote the cell dispersion by reducing cell-cell or cell-matrix interactions and further improving cell migration.In this study,the TFF3 binding protein,alde-keto reductase 1C 1(AKR1C1),was screened by yeast two-hybrid.AKR1C1 is a member of the aldose reductase family,in addition to catalysis,but also affect cell sensitivity,as well as cell growth,apoptosis and metastasis.AKR1C1 increased gastric cancer chemotherapy resistance,poor prognosis.Increased expression of AKR1C1 in chemotherapy resistant gastric cancer cells,promote gastric cancer cell proliferation,antagonize gastric cancer cell apoptosis.This study focused on the combination of TFF3 and AKR1C1 in gastric cancer cells,and further explored the regulation of gastric cancer cell metastasis and specific molecular mechanisms.First,the expression characteristics of TFF3 and AKR1C1 in gastric carcinoma were identified by immunohistochemistry and quantitative PCR from the two levels of tissue level and cell level,that is,both were up-regulated in gastric cancer,followed by the construction of exogenous expression plasmid,Immunoprecipitation CO-IP further confirmed the binding of TFF3 to AKR1C1 in gastric cancer cells.Thirdly,TFF3 overexpression was observed in wild-type and gastric cancer cells expressing endogenous AKR1C1,and cell proliferation was detected by CCK8 cell activity assay.Transwell chamber and Woundhealing scratch test were used to detect the invasion and invasion of cells.Apoptosis was detected by apoptotic body test.The effect of AKR1C1 on the proliferation/invasion of gastric cancer cells was confirmed by TFF3.Finally,Western blotting was used to detect AKT Pathway activation level and expression of EMT-related marker protein in epithelial-mesenchymal transition.In conclusion,the expression of TFF3 and AKR1C1 in gastric cancer was up-regulated and correlated with each other,which affected the activation level of AKT pathway and promoted epithelial-mesenchymal transformation of EMT.Thus,AKR1C1 played a role in TFF3 promoting the invasion and invasion of gastric cancer cells,The two jointly promote the occurrence and development of gastric cancer.Therefore,this topic complements TFF3 through its binding protein-mediated regulation of the development of gastric cancer in the new mechanism,and suggest that AKR1C1 may be used as a new target in the clinical diagnosis and treatment of gastric cancer. |
