Produção Nacional
Revisado por pares
Downregulation of RKIP Is Associated with Poor Outcome and Malignant Progression in Gliomas
2012; Public Library of Science; Volume: 7; Issue: 1 Linguagem: Inglês
10.1371/journal.pone.0030769
ISSN1932-6203
AutoresOlga Martinho, Sara Granja, Teresa Jaraquemada, Cláudia Caeiro, Vera Miranda‐Gonçalves, Mrinalini Honavar, Paulo Costa, Margarida Damasceno, Marsha Rich Rosner, José Manuel Lopes, Rui Manuel Reis,
Tópico(s)Mechanisms of cancer metastasis
ResumoMalignant 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.
Referência(s)