Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer

P. H. Su, Y. W. Lin, R. L. Huang, Y. P. Liao, H. Y. Lee, H. C. Wang, T. K. Chao, C. K. Chen, M. W Y Chan, T. Y. Chu, M. H. Yu, H. C. Lai

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalOncogene
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 3 2013
Externally publishedYes

Keywords

  • cervical cancer
  • DNA methyltransferase
  • metastasis; methylation
  • mitogen-activated protein kinase
  • protein tyrosine phosphatase receptor type R

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Su, P. H., Lin, Y. W., Huang, R. L., Liao, Y. P., Lee, H. Y., Wang, H. C., Chao, T. K., Chen, C. K., Chan, M. W. Y., Chu, T. Y., Yu, M. H., & Lai, H. C. (2013). Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer. Oncogene, 32(1), 15-26. https://doi.org/10.1038/onc.2012.29