Background
Integrin alpha 2 (ITGA2) is highly expressed in various cancers. ITGA2 up regulation promotes tumor proliferation, invasion, migration, and angiogenesis and ITGA2 is a poor prognostic factor in many tumors. However, the mechanism underlying its role in esophageal squamous cell carcinoma (ESCC) is unknown.
Conclusion
Our findings indicated that in ESCC, ITGA2 promotes proliferation, invasion and migration, while inhibiting apoptosis and promoting EMT in ESCC, possibly via FAK/AKT phosphorylation. These findings highlight the therapeutic value of ITGA2 in ESCC.
Methods
The expression profile of ITGA2 in ESCC was analyzed using the Gene expression profiling interactive analysis (GEPIA). ESCC tissues were analyzed by real time PCR (RT-qPCR) and immunohistochemistry to verify ITGA2 expression. The impact of ITGA2 on the clinicopathological characteristics was explored using a chi-square test. Apoptosis, Transwell, colony formation, and wound healing assays were conducted to characterize the roles of ITGA2 in ESCC. Its impact on tumorigenesis was further examined using a tumor xenograft model. The expression of proteins associated with the epithelial-mesenchymal Transition (EMT) and focal adhesion kinase (FAK)/AKT pathway and regulated by ITGA2 was evaluated with Western blot analysis. The Akt inhibitor MK-2206 was used to explore the interaction of ITGA2 with the FAK/Akt pathway.
Results
ITGA2 was upregulated in ESCC tissues and related to lymph node metastasis as well as TNM stage. In vitro experimental models revealed that ITGA2 promotes proliferation, invasion, and migration, and inhibits apoptosis. In vivo experiments show that ITGA2 promotes ESCC proliferation. Additionally, Western blot analysis revealed that ITGA2 silencing inhibits FAK/AKT signaling and suppresses EMT, while its overexpression activates FAK/AKT signaling and promotes EMT. Moreover, treatment with the AKT inhibitor MK-2206 successfully repressed the progression of ESCC caused by ITGA2 overexpression.