Role of CHD7 chromatin remodeler protein in glioblastoma stem cells (GSCs) maintenance and radioresistance

• Grant number: 14/21614-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2015
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Raquel Arminda Martinez Machado
• Supervisor: Michael Weller
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University Hospital Zurich, Switzerland
• Associated to the scholarship: 13/23271-0 - Role of the CHD7 chromatin remodeler protein in human brain tumor cells, BP.DR

Abstract

Since it was found that CHD7 mutations are the major cause of the CHARGE syndrome in humans, this gene has been further studied from the functional point of view, however, no reports are yet available demonstrating the association of the corresponding protein with brain tumor development or maintenance. Previous experiments performed in our laboratory suggest that CHD7 mRNA is present, at high levels, in different lineages of glioma cell lines, as well as in patient samples of different malignancy grades, when compared to normal brain. Moreover, TCGA database analysis shows that CHD7 expression levels positively correlated to the expression of several stem cell-related genes. Cancer stem cells or tumor initiating cells are a subset of tumor cells possessing stem cell properties, such as self-renewal and multi-lineage differentiation, which are functionally highly efficient at initiating tumor xenografts in vivo. Glioblastoma stem cells (GSCs) have been shown to be resistant to conventional chemo- and radiotherapy, being thought to play a critical role in tumor initiation, infiltration and recurrence. To understand the role of CHD7 in human brain tumor, this project aims to investigate whether CHD7 is functionally associated with maintenance of GSCs. Additionally, we will verify the effect of lentivirus-mediated CHD7 downregulation and overexpression in vivo by orthotopical xenotranplantation of GSCs in nude mice. We expect that our research will greatly contribute to a better understanding of the molecular mechanisms underlying the role of CHD7 chromatin remodeler protein and provide unprecedented insights into cellular pathways and gene networks associated with cancer. (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)

MACHADO, RAQUEL A. C.; SCHNEIDER, HANNAH; DEOCESANO-PEREIRA, CARLOS; LICHTENSTEIN, FLAVIO; ANDRADE, FERNANDO; FUJITA, ANDRE; TROMBETTA-LIMA, MARINA; WELLER, MICHAEL; BOWMAN-COLIN, CHRISTIAN; SOGAYAR, MARI CLEIDE. CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature. SCIENTIFIC REPORTS, v. 9, MAR 8 2019. (13/23271-0, 14/21614-0)