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Comparative analysis of the Reck tumor suppressor gene role in glioblastoma stem cell sub-population and in normal neural stem cells.

Grant number: 15/26328-8
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2016
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Mari Cleide Sogayar
Grantee:Marina Trombetta Lima
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/18277-7 - ANALYSIS OF THE RECK TUMOR SUPPRESSOR GENE'S ROLE IN ASYMMETRIC CELL DIVISION, BE.EP.PD

Abstract

Glioblastoma multiforme (GBM) is the most common and lethal type of tumor of the central nervous system.. The glioblastoma stem-like cells (GSCs) represent the most undifferentiated and aggressive state of GBM malignant cells, being postulated to be responsible for reinitiating the tumorigenic process after the standard current therapy. In addition, the complex GBM intra-tumor heterogeneity highlights the contribution of different cell types such as neural stem cells and their derivatives in the genesis of this tumor. The RECK canonical protein suppresses cellular invasion, angiogenesis, and metastasis, but its mechanism of action is not yet fully understood. In order to contribute to better understanding of the complex RECK expression pattern, alternative spliced RECK transcripts were recently isolated and described by our group, who showed that the balance between the variants has an informative potential for GBM prognosis. Interestingly, the functional study of one of them, namely, RECK-B, suggests it has a pro-oncogenic activity. Furthermore, Reck depletion leads to precocious neuro-differentiation in mice brain during embryonic development, through the modulation of the Nocht pathway. Reck expression is higher in the dentate gyrus of adult murine brain, giving rise to the hypothesis about Reck's role in maintenance of NSCs in the undifferentiated state or their commitment to different differentiation pathways. Through meta-analysis, our preliminary data show that RECK expression, without distinction among its variants, is unexpectedly higher in CD133-positive tumor cells. In this context, we propose to evaluate the influence of canonical RECK and RECK-B in NSCs and its derivatives as well as in GSCs behavior and in the GBM tumorigenic process.

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORETTI, ISABELE F.; LERARIO, ANTONIO M.; TROMBETTA-LIMA, MARINA; SOLA, PAULA R.; SOARES, ROSELI DA SILVA; OBA-SHINJO, SUELI M.; MARIE, SUELY K. N.. Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. SCIENTIFIC REPORTS, v. 11, n. 1, . (13/02162-8, 16/14695-9, 15/26328-8, 04/12133-6)
SPINDOLA, ADAUTO; TARGA, ADRIANO D. S.; RODRIGUES, LAIS SOARES; WINNISCHOFER, SHEILA MARIA BROCHADO; LIMA, MARCELO M. S.; SOGAYAR, MARI CLEIDE; TROMBETTA-LIMA, MARINA. Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model. Molecular Neurobiology, v. 57, n. 2, p. 837-847, . (16/18277-7, 16/05311-2, 15/26328-8)
MOREIRA FRANCO, YOLLANDA E.; ALVES, MARIA JOSE; UNO, MIYUKI; MORETTI, ISABELE FATTORI; TROMBETTA-LIMA, MARINA; DE SIQUEIRA SANTOS, SUZANA; DOS SANTOS, ANCELY FERREIRA; ARINI, GABRIEL SANTOS; BAPTISTA, MAURICIO S.; LERARIO, ANTONIO MARCONDES; et al. Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness. CANCER & METABOLISM, v. 9, n. 1, . (13/02162-8, 20/02988-7, 15/26328-8, 13/07937-8, 04/12133-6)
ASSIS-RIBAS, THAIS; FORNI, MARIA FERNANDA; BROCHADO WINNISCHOFER, SHEILA MARIA; SOGAYAR, MARI CLEIDE; TROMBETTA-LIMA, MARINA. Extracellular matrix dynamics during mesenchymal stem cells differentiation. Developmental Biology, v. 437, n. 2, p. 63-74, . (15/26328-8, 16/05311-2, 16/22298-0, 16/18277-7, 15/25776-7)
TROMBETTA-LIMA, MARINA; ROSA-FERNANDES, LIVIA; ANGELI, CLAUDIA B.; MORETTI, ISABELE F.; FRANCO, YOLLANDA M.; MOUSESSIAN, ADALIANA S.; WAKAMATSU, ALDA; LERARIO, ANTONIO M.; OBA-SHINJO, SUELI M.; PASQUALUCCI, CARLOS A.; et al. Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma. JOURNAL OF PROTEOME RESEARCH, v. 20, n. 10, p. 4693-4707, . (14/06863-3, 16/14695-9, 15/26328-8)
TROMBETTA-LIMA, MARINA; ASSIS-RIBAS, THAIS; CINTRA, RICARDO C.; CAMPEIRO, JOANA D.; GUERREIRO, JULIANO R.; WINNISCHOFER, SHEILA M. B.; NASCIMENTO, ISIS C. C.; ULRICH, HENNING; HAYASHI, MIRIAN A. F.; SOGAYAR, MARI C.. Impact of Reck expression and promoter activity in neuronal in vitro differentiation. MOLECULAR BIOLOGY REPORTS, v. 48, n. 2, . (18/20014-0, 16/05311-2, 18/07366-4, 14/50891-1, 19/13112-8, 15/26328-8, 16/18277-7, 12/50880-4, 17/02413-1)
JACOMASSO, THIAGO; RIBAS, HENNRIQUE TABORDA; TROMBETTA-LIMA, MARINA; KONIG, MICHELLE SILBERSPITZ; TRINDADE, EDVALDO SILVA; MARTINEZ, GLAUCIA REGINA; SOGAYAR, MARI CLEIDE; WINNISCHOFER, SHEILA MARIA BROCHADO. The alternatively spliced RECK transcript variant 3 is a predictor of poor survival for melanoma patients being upregulated in aggressive cell lines and modulating MMP gene expression in vitro. Melanoma Research, v. 30, n. 3, p. 223-234, . (16/18277-7, 16/05311-2, 15/26328-8)

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