EphA10 Drives Tumor Progression And Decrease Of Immune Response By Regulating The MAPK/ERK Cascade In Lung Adenocarcinoma

Backgrounds: Lung adenocarcinoma is the most frequent histological type among patients with lung cancer.Ephrin receptor A10(EphA10),a member of the receptor tyrosine kinase family,has been reported to participate in tumor progression,but its role in lung adenocarcinoma(LUAD)remains unknown.Methods: Immunohistochemistry staining and Real-time PCR were employed to determine the expression of EphA10 in clinical LUAD samples.EphA10 silencing or overexpression in LUAD cells was achieved by transduction of lentivirus.The effects of EphA10 on LUAD cells were evaluated by CCK-8,Ed U staining,flow cytometry,Transwell,and western blot.The in vivo tumor growth was assessed in the xenograft mice model.Results: EphA10 was highly expressed in LUAD tissues and was correlated with the advanced disease stage of patients.Mechanically,silencing of EphA10 suppressed proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of LUAD cells.Furthermore,EphA10 knockdown significantly reduced the PD-L1 expression in LUAD cells and enhanced NK cell-mediated anti-tumor effects.Additionally,EphA10 activated MAPK/ERK pathway,and U0126,an inhibitor of MEK,markedly reversed the promoting impacts of EphA10 overexpression on LUAD cells.Consistently,results from subcutaneous tumor xenografts in nude mice confirmed that EphA10 knockdown significantly inhibited tumor growth in vivo.Conclusions: This work demonstrates that silencing of EphA10 inhibits malignant phenotypes and immune evasion of LUAD cells by suppressing the activation of the MAPK/ERK signaling pathway,implying that EphA10 has the potential to be a therapeutic target in treating LUAD.