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Investigating Rho GTPases pathways in the response of glioma cell lines to genotoxic stress

Grant number: 17/01451-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2017
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Deborah Schechtman
Grantee:Yuli Thamires Magalhães
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glioblastoma is the most common primary brain tumor, and despite the combination of surgery with radio and chemotherapy, the prognosis is still very poor. The increase in cell proliferation and migration of these tumors is directly related to their aggressiveness, which has recently been related to the Rho GTPases pathways. Functional evidence of the RhoA roles in gliomas has been demonstrated for ROCK inhibition, leading to Rac1 activation and increased invasion and cell migration. In addition, it has already been demonstrated that Rho GTPases act on mechanisms of recognition and repair of DNA damage in tumor cells. For example, our group has recently showed that RhoA activity in human tumor lines regulates the sensitivity of these cells when exposed to ionizing gamma and non-ionizing ultraviolet radiation, affecting DNA repair pathways such as HR, NHEJ and NER through still unknown molecular mechanisms. Thus, this project aims to investigate the Rho GTPase signaling pathway, including its downstream components and the actin cytoskeleton polymerization, in glioblastoma cells after being subjected to DNA damage. In addition, we also intend to investigate whether the involvement of the Rho pathway depends or not on the p53 tumor suppressor protein and on the oxidative stress promoted by the clinically employed treatments, such as ³-radiation and cisplatin. Finally, we aim to use the results of this research to further elucidate the signaling pathways involving Rho GTPases and to show that both the components of the aforementioned pathways, as well as the actin cytoskeleton itself, are promising targets for the development of treatments against the different types of glioblastomas, or even the improvement of existing treatments. (AU)

Scientific publications
(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)
FACHI, JOSE LUIS; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; DA SILVA, BRUNA KARADI; CORREA, RENAN OLIVEIRA; PEREIRA DE ANDRADE, MIRELLA CRISTINY; DA FONSECA, DENISE MORAIS; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE SALES E SOUZA, ERICKA LORENNA; MARTINS, FLAVIANO DOS SANTOS; SATO GUIMA, SUZANA EIKO; THOMAS, ANDREW MALTEZ; SETUBAL, JOAO CARLOS; MAGALHAES, YULI THAMIRES; FORTI, FABIO LUIS; CANDREVA, THAMIRIS; RODRIGUES, HOSANA GOMES; DE JESUS, MARCELO BISPO; CONSONNI, SILVIO ROBERTO; FARIAS, ALESSANDRO DOS SANTOS; VARGA-WEISZ, PATRICK; RAMIREZ VINOLO, MARCO AURELIO. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. CELL REPORTS, v. 27, n. 3, p. 750+, APR 16 2019. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.