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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival

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Author(s):
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Lopes, M. H. [1, 2, 3, 4] ; Santos, T. G. [2, 3, 4] ; Rodrigues, B. R. [2, 3, 4] ; Queiroz-Hazarbassanov, N. [2, 3, 4] ; Cunha, I. W. [5] ; Wasilewska-Sampaio, A. P. [2, 3, 4] ; Costa-Silva, B. [2, 3, 4] ; Marchi, F. A. [2, 3, 4, 6] ; Bleggi-Torres, L. F. [7, 8] ; Sanematsu, P. I. [9] ; Suzuki, S. H. [9] ; Oba-Shinjo, S. M. [10] ; Marie, S. K. N. [10] ; Toulmin, E. [11] ; Hill, A. F. [11] ; Martins, V. R. [12, 2, 3, 4]
Total Authors: 16
Affiliation:
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[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil
[2] AC Camargo Canc Ctr, Int Res Ctr, BR-01508010 Sao Paulo - Brazil
[3] CNPq MCT FAPESP, Nat Inst Translat Neurosci, Sao Paulo - Brazil
[4] CNPq MCT FAPESP, Natl Inst Oncogen, Sao Paulo - Brazil
[5] AC Camargo Canc Ctr, Dept Pathol, BR-01508010 Sao Paulo - Brazil
[6] Univ Sao Paulo, Inst Math & Stat, Interinst Grad Program Bioinformat, Sao Paulo - Brazil
[7] Univ Fed Parana, Dept Pathol, BR-80060000 Curitiba, Parana - Brazil
[8] Pele Pequeno Principe Res Inst, Curitiba, Parana - Brazil
[9] AC Camargo Canc Ctr, Dept Neurosurg, BR-01508010 Sao Paulo - Brazil
[10] Univ Sao Paulo, Sch Med, Dept Neurol, BR-05508 Sao Paulo - Brazil
[11] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic - Australia
[12] Ludwig Inst Canc Res, Sao Paulo - Brazil
Total Affiliations: 12
Document type: Journal article
Source: Oncogene; v. 34, n. 25, p. 3305-3314, JUN 2015.
Web of Science Citations: 12
Abstract

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. (AU)

FAPESP's process: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches
Grantee:Vilma Regina Martins
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/20796-6 - Prion protein and its STI1 ligands and laminin: possible implications in Alzheimer's Disease
Grantee:Ana Paula Wasilewska Sampaio
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/19019-0 - Regulation of STAT3 activity and the role of secreted STI1/Hop protein in glioblastoma multiforme
Grantee:Bruna Roz Rodrigues
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
Grantee:Suely Kazue Nagahashi Marie
Support type: Research Projects - Thematic Grants
FAPESP's process: 07/08410-2 - Role of the STI1-PrPc interaction in the biology of neural stem cells: physiological and tumoral contexts
Grantee:Marilene Hohmuth Lopes
Support type: Regular Research Grants