التفاصيل البيبلوغرافية
| العنوان: |
Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. |
| المؤلفون: |
Lopes, M H, Santos, T G, Rodrigues, B R, Queiroz-Hazarbassanov, N, Cunha, I W, Wasilewska-Sampaio, A P, Costa-Silva, B, Marchi, F A, Bleggi-Torres, L F, Sanematsu, P I, Suzuki, S H, Oba-Shinjo, S M, Marie, S K N, Toulmin, E, Hill, A F, Martins, V R |
| المصدر: |
Oncogene; 6/18/2015, Vol. 34 Issue 25, p3305-3314, 10p, 1 Chart, 5 Graphs |
| مصطلحات موضوعية: |
GLIOBLASTOMA multiforme, PRIONS, HSP70 heat-shock proteins, NERVOUS system, ASTROCYTOMAS, PHOSPHOINOSITIDES, PHOSPHATIDYLINOSITOL 3-kinases, GENE knockout, DIAGNOSIS |
| مستخلص: |
Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrPC) triggers a large number of trophic effects in the nervous system. We found that both PrPC and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrPC and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrPC binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrPC binding site (HOP230-245) abrogates this effect. PrPC knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrPC-HOP engagement is a promising approach for GBM therapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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