Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer.
Oncogene
; 32(1): 15-26, 2013 Jan 03.
Article
en En
| MEDLINE
| ID: mdl-22330137
ABSTRACT
Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference. Using methyl-DNA immunoprecipitation coupled with microarray analysis, we found that the protein tyrosine phosphatase receptor type R (PTPRR) was silenced through DNMT3B-mediated methylation in the cervical cancer. PTPRR inhibited p44/42 MAPK signaling, the expression of the transcription factor AP1, human papillomavirus (HPV) oncogenes E6/E7 and DNMTs. The methylation status of PTPRR increased in cervical scrapings (n=358) in accordance with disease severity, especially in invasive cancer. Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Neoplasias del Cuello Uterino
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Sistema de Señalización de MAP Quinasas
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Silenciador del Gen
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Epigénesis Genética
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Proteínas Tirosina Fosfatasas Clase 7 Similares a Receptores
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Metástasis de la Neoplasia
Límite:
Female
/
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Taiwán