Alpha Protein Kinase 2 Promotes Esophageal Cancer via Integrin Alpha 11.

Background: As a common disease around the world, esophageal cancer (EC) primarily includes two subclasses: esophageal adenocarcinoma and esophageal squamous cell carcinoma. Mortality has been rising over the years; hence, exploring the mechanism of EC development has become critical. Among the alpha protein kinases, alpha protein kinase 2 (ALPK2) presumably has a connection with EC, but it has never been revealed before.

Methods: In this study, IHC analysis was used for ALPK2 expression quantification in ES tissues. TE-1 and Eca-109, which are both human EC cell lines, were used for analysis of cell proliferation, migration, apoptosis, and colony formation.

Results: ALPK2 was found to have an abundant expression within EC tissues ( < 0.001), as well as in the two selected human EC cell lines ( < 0.05). The data showed that ALPK2 depletion suppressed EC cell proliferation, migration, and colony formation, meanwhile stimulating apoptosis ( < 0.001). The experiments also displayed inhibitory effects caused by ALPK2 depletion on EC tumorigenesis ( < 0.001). It was further validated that ALPK2 depletion made the phosphorylation of Akt and mTOR, as well as CDK6 and PIK3CA levels downregulated ( < 0.001). Mechanistically, we identified integrin alpha 11 (ITGA11) as a downstream gene of ALPK2 regulating EC. More importantly, we found that ITGA11 elevation promoted cell proliferation and migration and rescued the suppression effects caused by ALPK2 depletion ( < 0.001).

Conclusions: ALPK2 promotes esophageal cancer via integrin its downstream gene alpha 11; ALPK2 can potentially act as a target for the treatment of EC.