부산대학교 도서관

Suppressor of cytokine signaling (SOCS) proteins are the negative regulators in cellular signal transduction system. SOCS family proteins consisting of 8 proteins (CIS and SOCS1-7) down-regulate JAK/STAT protein activity to maintain cytokine functions at proper levels. Recent reports showed that SOCS1 can affect multiple signaling pathways to regulate cell survival, apoptosis, cancer development and progression. The present study was aimed to investigate various effects of SOCS1 protein on the tumor suppressive function employing colon cancer models. It was found that SOCS1 promoted gamma radiation-induced HCT116 colon cancer cell apoptosis and exhibited suppressive effects on tumor cell migration and invasion. Notably SOCS1 over-expression and knock-out inversely regulated expression of the epithelial mesenchymal transition (EMT) markers such as E-cadherin and vimentin along with modest morphological changes of cells from epithelial to fibroblast shape, representing EMT process. Down-regulation of signaling pathways involved in tumor growth and invasion including Src, PI3K/Akt, Erk, NF-kB and β-catenin was evident in SOCS1-overexpressing tumor cells. Supporting these in vitro effects, SOCS1 further inhibited the growth of implanted colon cancer cells in nude mice upon radiation therapy and exhibited suppressive effects on the lung metastasis of injected tumor cells in vivo. Taken together these results strongly suggest the potential anti-tumor function of SOCS1. Thus SOCS1 may serve not only a useful predictive factor for radiation response but also a molecular target with a therapeutic potential in human colon cancers.