Molecular Mechanism And Clinical Significance Of GLUT4 Expression Induced By Fusobacterium Nucleatum In Esophageal Squamous Cell Carcinoma

Background: Previous studies of our team have confirmed that Fusobacterium nucleatum（Fn）is closely related to the malignant progression of esophageal squamous cell carcinoma（ESCC）.Many pathogenic microorganisms can provide favorable material conditions for their long-term colonization by enhancing glucose metabolism of host cells.Glucose transporter 4（GLUT4）,which mediates glucose transmembrane transport,is a key factor in glucose uptake by tumor cells.We hypothesized that Fn could promote glucose uptake by ESCC cells by activating GLUT4.Objective: To explore the regulatory mechanism and role of Fn on GLUT4 in ESCC cells,and analyze the effect of FN induction on GLUT4 on the survival and prognosis of ESCC patients,so as to provide new ideas and treatment methods for ESCC treatment.Methods:1.Establishment of ESCC cell lines with GLUT4 knockdown;2.The effects of Fn infection on glucose metabolism and in vitro proliferation of parental cell lines and GLUT4 knockdown cell lines were detected;3.The effect of Fn infection on tumorigenicity of parent cell lines and GLUT4 knockdown cell lines in vivo was detected by subcutaneous tumorigenicity assay;4.Fn infection and GLUT4 expression in ESCC tissues were detected by RNAscope and immunohistochemistry;5.Chi-square test was used to analyze the correlation between Fn induced GLUT4 expression and clinicopathological features of ESCC patients;6.Survival curves were drawn using the Kaplan-meier method;log-rank test to analyze differences in survival time;7.SPSS 26.0 software was used for data analysis.Test level α=0.05.P < 0.05 considered the difference to be statistically significant;Results:1.The ESCC cell line sh GLUT4 with GLUT4 knockdown was successfully established;2.Fn can enhance glucose metabolism and proliferation of ESCC cells by inducing high expression of GLUT4;3.Fn can enhance in vivo tumorigenicity of ESCC cells by inducing high expression of GLUT4;4.The high expression of Fn infection and GLUT4 was consistent in ESCC tissues,but negative expression of Fn infection and GLUT4 was found in adjacent tissues;5.The ESCC patients in the Fn induced GLUT4 high expression positive group were mostly male patients who smoked and drank,and the tumor differentiation was low,the invasion depth was deep,the lymph node metastasis was early,and the clinical stages were mostly stage III/IV;6.The 5-year survival rate of ESCC patients with high expression of GLUT4 induced by Fn was significantly shortened.Conclusions:After Fn infection and colonization,it can enhance the glucose metabolism of ESCC cells by inducing the high expression of GLUT4,promote its malignant progression and affect the prognosis.