Loss of RACK1 promotes metastasis of gastric cancer by inducing a miRNA-302c / IL-8 signaling loop
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la perte d'expression du gène RACK1 favorise le processus métastatique d'une tumeur gastrique
Gastric cancer remains the third leading cause of cancer-related mortality worldwide, and invasion and metastasis of gastric cancer represent the major reason for its poor prognosis. In this study, we found that loss of the receptor for activated C-kinase 1 (RACK1) promoted the metastasis of gastric cancer by enhancing the autocrine of interleukin (IL)-8 in vitro and in vivo. MicroRNA array identified that RACK1 modulated the expression of a series of microRNAs including microRNA-302 cluster, and RACK1 modulated the IL-8 expression and tumor invasion through microRNA-302c. Moreover, up-regulation of IL-8 in turn decreased the level of microRNA-302c and induced IL-8 expression in feedback manner. Tissue microarray also indicated that RACK1 was correlated with invasion/metastasis phenotype, IL-8 expression as well as five-year survival in clinical cases of gastric cancer. Together, our results imply that loss of RACK1 in gastric cancer links epigenetics to inflammatory cytokines to promote tumor metastasis.