PRRX2 as a novel TGF-ß-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer.
Mol Carcinog
; 55(12): 2247-2259, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-26824226
ABSTRACT
TGF-ß and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-ß biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-ß continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-ß-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-ß and identified TGF-ß-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-ß-induced invasion and EMT in breast cancer. © 2016 Wiley Periodicals, Inc.
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Base de dados:
MEDLINE
Assunto principal:
Mama
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Neoplasias da Mama
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Fator de Crescimento Transformador beta
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Proteínas de Homeodomínio
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Invasividade Neoplásica
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article