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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.)

Guanylate-binding protein-1 is a potential new therapeutic target for triple-negative breast cancer

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Quintero, Melissa [1] ; Adamoski, Douglas [1, 2] ; dos Reis, Larissa Menezes [1, 2] ; Rodrigues Ascencao, Carolline Fernanda [1, 2] ; Sousa de Oliveira, Krishina Ratna [1, 2] ; Goncalves, Kaliandra de Almeida [1] ; Dias, Marilia Meira [1] ; Carazzolle, Marcelo Falsarella [3] ; Gomes Dias, Sandra Martha [1]
Total Authors: 9
[1] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil
[2] Univ Campinas UNICAMP, Grad Program Genet & Mol Biol, Inst Biol, Campinas, SP - Brazil
[3] Univ Campinas UNICAMP, LGE, Inst Biol, Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BMC CANCER; v. 17, NOV 7 2017.
Web of Science Citations: 8

Background: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression (ESR and PGR, respectively) and an absence of human epithelial growth factor receptor (ERBB2) amplification. Approximately 15-20% of breast malignancies are TNBC. Patients with TNBC often have an unfavorable prognosis. In addition, TNBC represents an important clinical challenge since it does not respond to hormone therapy. Methods: In this work, we integrated high-throughput mRNA sequencing (RNA-Seq) data from normal and tumor tissues (obtained from The Cancer Genome Atlas, TCGA) and cell lines obtained through in-house sequencing or available from the Gene Expression Omnibus (GEO) to generate a unified list of differentially expressed (DE) genes. Methylome and proteomic data were integrated to our analysis to give further support to our findings. Genes that were overexpressed in TNBC were then curated to retain new potentially druggable targets based on in silico analysis. Knocking-down was used to assess gene importance for TNBC cell proliferation. Results: Our pipeline analysis generated a list of 243 potential new targets for treating TNBC. We finally demonstrated that knock-down of Guanylate-Binding Protein 1 (GBP1), one of the candidate genes, selectively affected the growth of TNBC cell lines. Moreover, we showed that GBP1 expression was controlled by epidermal growth factor receptor (EGFR) in breast cancer cell lines. Conclusions: We propose that GBP1 is a new potential druggable therapeutic target for treating TNBC with enhanced EGFR expression. (AU)

FAPESP's process: 12/11577-4 - Studies of the metabolic alterations related to the PI3K-Akt pathway and RAS oncogene co-activation.
Grantee:Marília Meira Dias
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/17820-3 - Post-transcriptional regulation of glutaminase enzyme by HuR and its relationship with high glutaminolytic levels in tumors
Grantee:Douglas Adamoski Meira
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 14/06512-6 - Epigenetic study of histone demethylases enzymes Fe (II) and ±-ketoglutarate dependent of the jumonji family in the context of tumoral metabolism and glutaminase activity
Grantee:Krishina Ratna Sousa de Oliveira
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 09/53853-5 - Acquisition of a high-performance platform for computational analyses applied to the field of medicine
Grantee:Wilson Araújo da Silva Junior
Support type: Multi-user Equipment Program
FAPESP's process: 15/25832-4 - Metabolic regulation of genetic and epigenetic control of gene expression
Grantee:Sandra Martha Gomes Dias
Support type: Regular Research Grants
FAPESP's process: 14/18061-9 - Study of alternative anaplerotic sources of the TCA as new targets against triple-negative breast cancer
Grantee:Larissa Menezes dos Reis
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/23510-4 - Understanding how PI3K/AKt/mTOR and AMPK signaling pathways affect glutaminase activity.
Grantee:Carolline Fernanda Rodrigues Ascenção
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/15968-3 - Understanding the glutaminase functional regulation and the development of inhibitors as new approaches to cancer therapy
Grantee:Sandra Martha Gomes Dias
Support type: Regular Research Grants
FAPESP's process: 12/09452-9 - Transcriptome and metabolomic studies of cancer cells as a tool for understanding the metabolic adaptation process
Grantee:Melissa Quintero Escobar
Support type: Scholarships in Brazil - Doctorate (Direct)