| http://purl.uniprot.org/citations/20855151 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20855151 | http://www.w3.org/2000/01/rdf-schema#comment | "Accumulating evidence suggests that Raf kinase inhibitor protein (RKIP), which negatively regulates multiple signaling cascades including the Raf and nuclear factor-κB (NF-κB) pathways, functions as a metastasis suppressor. However, the basis for this activity is not clear. We investigated this question in a panel of breast cancer, colon cancer and melanoma cell lines. We found that RKIP negatively regulated the invasion of the different cancer cells through three-dimensional extracellular matrix barriers by controlling the expression of matrix metalloproteinases (MMPs), particularly, MMP-1 and MMP-2. Silencing of RKIP expression resulted in a highly invasive phenotype and dramatically increased levels of MMP-1 and MMP-2 expression, while overexpression of RKIP decreased cancer cell invasion in vitro and metastasis in vivo of murine tumor allografts. Knockdown of MMP-1 or MMP-2 in RKIP-knockdown cells reverted their invasiveness to normal. In contrast, when examining migration of the different cancer cells in a two-dimensional, barrier-less environment, we found that RKIP had either a positive regulatory activity or no activity, but in no case a negative one (as would be expected if RKIP suppressed metastasis at the level of cell migration itself). Therefore, RKIP's function as a metastasis suppressor appears to arise from its ability to negatively regulate expression of specific MMPs, and thus invasion through barriers, and not from a direct effect on the raw capacity of cells to move. The NF-κB pathway, but not the Raf pathway, appeared to positively control the invasion of breast cancer cells. A regulatory loop involving an opposing relationship between RKIP and the NF-κB pathway may control the level of MMP expression and cell invasion."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.canlet.2010.08.012"xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Ren G."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Fenteany G."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Yeung K.C."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Barone L.M."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Beshir A.B."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/author | "Magpusao A.N."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/name | "Cancer Lett"xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/pages | "137-149"xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/title | "Raf kinase inhibitor protein suppresses nuclear factor-kappaB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression."xsd:string |
| http://purl.uniprot.org/citations/20855151 | http://purl.uniprot.org/core/volume | "299"xsd:string |
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