Our results therefore suggest that RKIP is a novel component of the Snail transcriptional regulatory network important for the progression and metastasis of cancer.
Western blot analysis of blast cells from patients with C-RAF germline mutations revealed loss of the tumor and metastasis suppressor RAF kinase inhibitor protein (RKIP).
Consistent with these results, in the orthotopic murine models, we observed that overexpression of RKIP in breast cancer cells impaired invasiveness and metastasis, whereas down-regulation of RKIP expression promoted invasiveness and metastasis.
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.
Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis.
In multivariable analysis, the relative risk for amplification was 2.09 (95% CI 1.4-3.1; P<0.001) and linked to more frequent BRAF mutation (P=0.015), overexpression of p-MAPK3/MAPK1 (P=0.012) and PLAU (P=0.048) and loss of metastasis suppressor protein PEBP1 (P=0.047).
An RKIP pathway metastasis signature (designated RPMS) derived from the complete signalling cascade predicts high metastatic risk better than the individual genes.
The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms.
The purpose of this study was to investigate the effect of Raf kinase inhibitor protein (RKIP) on the growth, proliferation, invasion and metastasis of triple-negative breast cancer (TNBC) cells to provide experimental evidence for developing future therapies against human TNBC.
Promotion of metastasis in response to miR-224 downregulation was associated with derepression of the stroma-associated RKIP target genes, CXCR4, MMP1, and OPN, which are involved in breast tumor metastasis to the bone.
GCA patients in stage III and IV, with positive UGIC family history, and hypermethylation and down-expression of RKIP were most likely to develop metastatic disease and also showed the worse survival.
Taken together, our results strongly suggest that EGCG regulates RKIP/ERK/NF-κB and/or RKIP/NF-κB/Snail and inhibits invasive metastasis in the AsPC-1 human pancreatic adenocarcinoma cell line.
The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear.