title: Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas.
abstract: Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. 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. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193) of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients.
authors.affiliation: Life and Health Sciences Research Institute, Health Sciences School, University of Minho, Braga, Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Martinho
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.forename: Teresa
authors.initials: T
authors.lastname: Jaraquemada
authors.forename: Cláudia
authors.initials: C
authors.lastname: Caeiro
authors.forename: Vera
authors.initials: V
authors.lastname: Miranda-Gonçalves
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.forename: Paulo
authors.initials: P
authors.lastname: Costa
authors.forename: Margarida
authors.initials: M
authors.lastname: Damasceno
authors.forename: Marsha R
authors.initials: MR
authors.lastname: Rosner
authors.forename: José M
authors.initials: JM
authors.lastname: Lopes
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002478:Cells, Cultured; D002642:Chick Embryo; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D049488:Phosphatidylethanolamine Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D034741:RNA, Small Interfering