Raf kinase inhibitor protein (RKIP) in cancer.
Raf kinase inhibitory protein (RKIP) was initially identified as phosphatidylethanolamine binding protein in bovine brain. It was later identified as a protein that inhibits Raf kinase activation of MEK. Further exploration has revealed that RKIP modulates several other signaling pathways including NF-κB and G-protein signaling. A gene array screen revealed that RKIP expression was low in a metastatic compared with non-metastatic prostate cancer cell line. Further experiments revealed that RKIP fits the criteria for a metastasis suppressor gene. RKIP expression has been shown to be downregulated in metastatic tissues, compared with non-metastatic tissue in multiple cancers, suggesting that loss of RKIP metastasis suppressor activity is a broad mechanism leading to metastasis. Additionally, loss of RKIP has been shown to impact therapy through conferring radioresistance and chemoresistance. Taken together, these data indicate understanding RKIP's contributions to cancer may lead to important therapeutic strategies to prevent metastasis and promote therapeutic efficacy.
Department of Urology, University of Michigan, RM 5308 Cancer Center, 1500 East Medical Center Dr, Ann Arbor, MI 48109, USA.
June
J
Escara-Wilke
Kam
K
Yeung
Evan T
ET
Keller
D000818:Animals; D016147:Genes, Tumor Suppressor; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000209:etiology; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D050796:STAT3 Transcription Factor