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

doi:10.1038/onc.2012.29

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

Graduate Institute of Clinical Medicine

Research output: Contribution to journal › Article › peer-review

58 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 language	English
Pages (from-to)	15-26
Number of pages	12
Journal	Oncogene
Volume	32
Issue number	1
DOIs	https://doi.org/10.1038/onc.2012.29
Publication status	Published - Jan 3 2013

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2012.29

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

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.",

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AU - Su, P. H.

AU - Lin, Y. W.

AU - Huang, R. L.

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AU - Lee, H. Y.

AU - Wang, H. C.

AU - Chao, T. K.

AU - Chen, C. K.

AU - Chan, M. W Y

AU - Chu, T. Y.

AU - Yu, M. H.

AU - Lai, H. C.

PY - 2013/1/3

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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