NFAT5 Regulates IL8 to Promote Cell Growth and Migration in Non-Small Cell Lung Cancer.

BACKGROUND: In certain types of solid tumors, nuclear factor of activated T cell 5 (NFAT5) plays critical roles in tumor development and progression. However, the subtle regulatory mechanism of NFAT5 in particularly lung cancer has not been well characterized. METHODS: In this report, we measured the levels of interleukin-8 (IL8) in NSCLC cell lines. The target gene of IL8 was verified by ChIP assay and Luciferase reporter assay. Moreover, the function and regulatory mechanism of IL8 in the progression of cancer were further investigated. RESULTS: ELISA assay showed that IL8 was significantly downregulated in NFAT5 silencing PC9 cells and HCC827 cells. NFAT5 silencing caused inhibiting effects on proliferation, migration, and invasion in NSCLC cell lines. Further analysis indicated that IL8 was a direct target gene of NFAT5, evidenced by the direct binding of NFAT5 to the promoter of IL8. Elevated IL8 further enhanced the activation of the canonical NF-κB pathway. DISCUSSION: Our findings provide new insight into the mechanism of NSCLC progression. NFAT5 promotes cell growth and motility by regulating IL8 directly in NSCLC cell lines. Elevated IL8 expression causes enhancement of the NF-κB signaling pathway partially through autocrine or paracrine effects. These findings provide a possible mechanism of the inflammatory environment on lung cancer progression.