Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Raf kinase inhibitory protein (RKIP) negatively regulates the MAP kinase (MAPK), G protein-coupled receptor kinase-2, and NF-kappaB signalling cascades. RKIP has been implicated as a metastasis suppressor for prostate cancer, but the mechanism is not known. Here, we show that RKIP inhibits invasion by metastatic breast cancer cells and represses breast tumour cell intravasation and bone metastasis in an orthotopic murine model. The mechanism involves inhibition of MAPK, leading to decreased transcription of LIN28 by Myc. Suppression of LIN28 enables enhanced let-7 processing in breast cancer cells. Elevated let-7 expression inhibits HMGA2, a chromatin remodelling protein that activates pro-invasive and pro-metastatic genes, including Snail. LIN28 depletion and let-7 expression suppress bone metastasis, and LIN28 restores bone metastasis in mice bearing RKIP-expressing breast tumour cells. These results indicate that RKIP suppresses invasion and metastasis in part through a signalling cascade involving MAPK, Myc, LIN28, let-7, and downstream let-7 targets. RKIP regulation of two pluripotent stem cell genes, Myc and LIN28, highlights the importance of RKIP as a key metastasis suppressor and potential therapeutic agent.
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PMID:Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. 1915 3

Raf kinase inhibitor protein (RKIP) is first identified as an interacting partner of Raf-1. RKIP expression is low or absent in several established cell lines derived from metastatic breast cancer, prostate cancer and melanoma cells. However, the functional role of RKIP in gastric cancer remains unclear. In this study, we employed human gastric cancer cell line SGC7901 as a model to reconstitute RKIP expression in gastric cancer cells. The growth curve and soft agar assay showed that RKIP inhibited the growth and clonogenicity of SGC7901 cells. Flow cytometry analysis showed that RKIP inhibited the cell cycle progression and induced the apoptosis of SGC7901 cells. Wound healing and transwell invasion assay showed that RKIP inhibited the migration and invasion of SGC7901 cells. Furthermore, we observed that RKIP inhibited the growth of SMGC7901 cells in xenografts in nude mice. Taken together, our in vitro and in vivo data demonstrate that RKIP modulates the proliferation, apoptosis, migration, invasion and tumorigenicity of SGC7901 cells. These results reveal the tumor suppressor role of RKIP in gastric cancer and suggest that RKIP may be new therapeutic target for gastric cancer.
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PMID:RKIP inhibits the malignant phenotypes of gastric cancer cells. 2325 89