Interleukin-22 promotes lung cancer cell proliferation and migration via the IL-22R1/STAT3 and IL-22R1/AKT signaling pathways

Lung cancer continues to be an enormous burden on current health care systems throughout the world, with more than a million deaths every year. Previous studies have shown that interleukin-22 (IL-22) promotes survival and resistance to chemotherapy in human lung cancer cells. However, the association of IL-22 expression with recurrence of lung cancer is still unclear. In this study, we found that expression of IL-22 was upregulated in tumor tissues and serum from patients with recurrent non-small cell lung cancer (NSCLC) as compared to primary NSCLC samples. Treatment with IL-22 promoted cell proliferation and enhanced migration and invasion in A549 and H125 cell lines. Furthermore, we revealed that phosphorylation of STAT3 and AKT was highly induced by treatment with IL-22 via IL-22R1. IL-22R1 was also consistently overexpressed in recurrent NSCLC tissues. Finally, we found that siRNA-mediated depletion of IL-22R1 completely abrogated the effects of IL-22 treatment on cell proliferation and migration activity in NSCLC cell lines. Our findings indicate that IL-22 and IL-22R1 may be novel therapeutic targets for treatment of advanced NSCLC.