کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2132077 | 1086672 | 2010 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line](/preview/png/2132077.png)
Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), as a novel IFN-β/RA-inducible gene product, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. Recently, it has been reported that the apoptotic effects and apoptosis-related gene induction of GRIM-19 can be attenuated by GW112, indicating that GRIM-19 and GW112 are involved in a common signal transduction pathway. To investigate the signaling mechanisms that link GRIM-19 to GW112 and their functional role in tumor cell invasion and metastasis, we utilized adenovirus-mediated overexpression of GRIM-19 in the gastric cancer SGC-7901 cell line. We observed that enhanced expression of GRIM-19 not only downregulated GW112 but also decreased NF-кB binding activity. As a result, we found that tumor cell adhesion, migration, invasion and liver metastasis were inhibited. Additionally, upregulation of GRIM-19 also suppressed secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, 9 and vascular endothelial growth factor (VEGF). These results indicate that GRIM-19 acts as an upstream regulator of GW112 to block NF-кB binding activity, thereby inhibiting gastric cancer cell migration, invasion and metastasis. We conclude that adenoviral transfer of the GRIM-19 gene may be an efficacious approach to controlling the invasion and metastasis of human gastric cancer.
Journal: Experimental Cell Research - Volume 316, Issue 13, 1 August 2010, Pages 2061–2070