ITGA2 Overexprssion Promotes Esophageal Squamous Cell Carcinoma Aggression Via FAK/AKT Signaling Pathway

Background:ITGA2 is highly expressed in many malignant tumors.Highly expressed ITGA2 plays a key role in promoting tumor proliferation,invasion,migration,and angiogenesis.Also,ITGA2 is a poor prognostic factor for tumors.However,the mechanism of ITGA2 as a significant factor in esophageal squamous cell carcinoma(ESCC)remains unclear.Methods: The GEPIA(Gene Expression Profiling Interactive Analysis)web toolwas used to analyze the expression of ITGA2 in ESCC.Clinical tissue specimens of ESCC were collected for q RT-PCR and immunohistochemical experiments to verify its expression.The relevanceof ITGA2 and clinical characteristics were analyzed.Functional assays,such as the colony formation assay,flow cytometry apoptosis experiment,transwell assay,and wound healing assay,wereused to study the biological role of ITGA2 in ESCC.Tumor xenograft model was used to study the effect of ITGA2 on tumor formation of ESCC in vivo.Western-Blot analysis was used to study the role of ITGA2 in FAK/AKT pathway and EMT phenotype changes.The Akt inhibitor MK-2206 was used to explore the interaction of ITGA2 with the FAK/ Akt pathway.Results: We found that ITGA2 was up-regulated in esophageal squamous cell carcinoma tissues and was associated with lymph node metastasis.In vitro experiments,ITGA2 promoted proliferation,invasion and migration,and inhibited apoptosis.In vivo experiments,ITGA2 promoted the proliferation,invasion and migration of heterotopic tumors.Additionally,the Western-Blot analysisindicated that silencing ITGA2 inhibited the FAK/AKT pathway and down-regulated the EMT phenotype,while overexpression of ITGA2 activated the FAK/AKT pathway and up-regulated the EMT phenotype.Moreover,treatment with the AKT inhibitor MK-2206 successfully repressed the progression of ESCC caused by ITGA2 overexpression.Conclusion: Our experiments discovered a new mechanism of ITGA2 in esophageal cancer.ITGA2 may up-regulate the EMT phenotype through phosphorylation of FAK/AKT,promote the proliferation,invasion and migration,and inhibit its apoptosisof ESCC.These findings support further research into ITGA2 as a potential therapeutic targetof ESCC.