Cyr61 overexpression induced by interleukin 8 via NF-kB signaling pathway and its role in tumorigenesis of gastric carcinoma in vitro.

Cyr61 (CCN1) is a multifunctional matricellular protein in bridging inflammation and cancer, involved in many biological functions such as tumorigenesis and carcinogenesis. The role of Cyr61 in gastric cancer (GC) has not been fully understood and needs to be investigated and clarified. We examined Cyr61 expression in 6 GC cell lines and stable transfection of recombinants in to BGC823 specifically down regulated the Cyr61 mRNA and protein expression shown by the analysis with western blot, RT-PCR, western blot and immunofluorescence assay. The cells treated with siRNA shown markedly reduced activity in growth, migration and invasion compared with parental BGC823 cells as well as mock transfectants. The Cyr61 deficient cells demonstrated significantly inhibited colony formation in soft agar and reduced tumorigenicity was showed in nude mice, NF-kB pathway evidently inactivated respectively. However, under the stimulation of IL-8, the siRNA-treated cells can restore the capacity of proliferation and invasion. IL-8 can induce the high expression of Cyr61 and MMP11 through NF-kB signal pathway. Silencing of Cyr61 can inhibit or minimize the proliferation and invasiveness of gastric cancer cell. The results imply that Cyr61 enhance the proliferation and invasion of gastric cancer cells and this process is partially modulated by the IL-8 up-regulation. Cyr61 may mediate the proliferation and development of gastric carcinoma.