EphA10 通过调控 MAPK/ERK 级联反应驱动肺腺癌的肿瘤进展和免疫逃逸

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, EdU staining, flow cytometry, Transwell, and Western blot. The in vivo tumor growth was assessed in the xenograft mice model. Results EphA10 was overexpressed in LUAD tissues. Higher EphA10 expression was observed in the tissues at the advanced tumor stage and was positively correlated with the EGFR.

Mechanistically, silencing of EphA10 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition of LUAD cells.

Additionally, EphA10 knockdown significantly reduced the PD-L1 expression in LUAD cells and enhanced NK cell-mediated anti-tumor effects.

Furthermore, EphA10 activated the 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 EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in LUAD, implying that EphA10 has the potential to be a therapeutic target in treating LUAD.