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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Brachyury Is Associated with Glioma Differentiation and Response to Temozolomide

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Autor(es):
Pinto, Filipe [1, 2, 3, 4] ; Costa, Angela M. [1, 2, 3, 5] ; Andrade, Raquel P. [6, 7, 8] ; Reis, Rui Manuel [9, 1, 2]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] ICVS 3Bs PT Govt Associate Lab, P-4710057 Braga - Portugal
[2] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, P-4710057 Braga - Portugal
[3] Univ Porto, I3S Inst Invest & Inovacao Saude, P-4200135 Porto - Portugal
[4] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Porto - Portugal
[5] Univ Porto, INEB Inst Biomed Engn, P-4200135 Porto - Portugal
[6] Univ Algarve, Ctr Biomed Res CBMR, P-8005139 Faro - Portugal
[7] Algarve Biomed Ctr, Campus Gambelas, Edificio 2 Ala Norte, P-8005139 Faro - Portugal
[8] Univ Algarve, Dept Med & Biomed Sci, P-8005139 Faro - Portugal
[9] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP - Brazil
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: NEUROTHERAPEUTICS; v. 17, n. 4, SI AUG 2020.
Citações Web of Science: 0
Resumo

Glioblastomas (GBMs) are the most aggressive tumor type of the central nervous system, mainly due to their high invasiveness and innate resistance to radiotherapy and chemotherapy, with temozolomide (TMZ) being the current standard therapy. Recently, brachyury was described as a novel tumor suppressor gene in gliomas, and its loss was associated with increased gliomagenesis. Here, we aimed to explore the role of brachyury as a suppressor of glioma invasion, stem cell features, and resistance to TMZ. Using gene-edited glioma cells to overexpress brachyury, we found that brachyury-positive cells exhibit reduced invasive and migratory capabilities and stem cell features. Importantly, these brachyury-expressing cells have increased expression of differentiation markers, which corroborates the results from human glioma samples andin vivotumors. Glioma cells treated with retinoic acid increased the differentiation status with concomitant increased expression of brachyury. We then selected TMZ-resistant (SNB-19) and TMZ-responsive (A172 and U373) cell lines to evaluate the role of brachyury in the response to TMZ treatment. We observed that both exogenous and endogenous brachyury activation, through overexpression and retinoic acid treatment, are associated with TMZ sensitization in glioma-resistant cell lines. In this study, we demonstrate that brachyury expression can impair aggressive glioma features associated with treatment resistance. Finally, we provide the first evidence that brachyury can be a potential therapeutic target in GBM patients who do not respond to conventional chemotherapeutic drugs. (AU)

Processo FAPESP: 12/19590-0 - Perfil mutacional de linhagens primárias de glioblastomas
Beneficiário:Rui Manuel Vieira Reis
Linha de fomento: Auxílio à Pesquisa - Regular