Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity

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art_GARCIA_Prostate_apoptosis_response_4_PAR4_expression_modulates_WNT_2017.PDF (1.36 MB)
Citações na Scopus
11
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPANDIDOS PUBL LTD
Autores
Citação
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.39, n.4, p.809-818, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment. Some of the top gene networks generated from the differentially expressed genes were related to the wingless-type MMTV integration 1 (WNT) canonical (WNT/-catenin) and non-canonical (-catenin-independent) pathways. The Human WNT signaling pathway RT2 profiler PCR array was used to validate the effects of PAR4 on the expression pattern of genes involved in the WNT pathway. CACNAD2A3, GDF5 and IL6 were upregulated and NANOG was downregulated in the MCF7 breast cancer cells expressing increased levels of PAR4 after treatment with docetaxel, likely indicating inactivation of the WNT/-catenin pathway. Upregulation of FGF7, LEF1 and TWIST1 indicated activation of the WNT/-catenin pathway. Although preliminary, our findings could be of particular interest for understanding the action of PAR4 in chemosensitivity, particularly to increase the specificity and effectiveness of drug treatment and overcome resistance to chemotherapy. Further studies are needed to better understand the biological roles of PAR4 in the regulation of WNT pathways in breast cancer cells in response to docetaxel and other chemotherapeutic agents.
Palavras-chave
prostate apoptosis response 4, breast cancer, chemosensitivity, docetaxel, WNT pathways, MCF7 cells
URI
https://observatorio.fm.usp.br/handle/OPI/20015
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03