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.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: P-H
authors.initials: PH
authors.lastname: Su
authors.forename: Y-W
authors.initials: YW
authors.lastname: Lin
authors.forename: R-L
authors.initials: RL
authors.lastname: Huang
authors.forename: Y-P
authors.initials: YP
authors.lastname: Liao
authors.forename: H-Y
authors.initials: HY
authors.lastname: Lee
authors.forename: H-C
authors.initials: HC
authors.lastname: Wang
authors.forename: T-K
authors.initials: TK
authors.lastname: Chao
authors.forename: C-K
authors.initials: CK
authors.lastname: Chen
authors.forename: M W Y
authors.initials: MW
authors.lastname: Chan
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chu
authors.forename: M-H
authors.initials: MH
authors.lastname: Yu
authors.forename: H-C
authors.initials: HC
authors.lastname: Lai
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D000097584:DNA Methyltransferase 3B
chemical_list: D014408:Biomarkers, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7; D000097584:DNA Methyltransferase 3B; C513469:PTPRR protein, human