title: A novel wnt regulatory axis in endometrioid endometrial cancer.
abstract: The Protocadherin 10 (PCDH10) is inactivated often by promoter hypermethylation in various human tumors, but its possible functional role as a tumor suppressor gene is not established. In this study, we identify PCDH10 as a novel Wnt pathway regulatory element in endometrioid endometrial carcinoma (EEC). PCDH10 was downregulated in EEC tumor cells by aberrant methylation of its promoter. Restoring PCDH10 levels suppressed cell growth and triggered apoptosis in EEC cells and tumor xenografts. Gene expression profiling revealed as part of the transcriptomic changes induced by PCDH10 a reduction in levels of MALAT1, a long noncoding RNA, that mediated tumor suppression functions of PCDH10 in EEC cells. We found that MALAT1 transcription was regulated by Wnt/β-catenin signaling via TCF promoter binding and PCDH10 decreased MALAT1 by modulating this pathway. Clinically, MALAT1 expression was associated with multiple parameters in patients with EEC. Taken together, our findings establish a novel PCDH10-Wnt/β-catenin-MALAT1 regulatory axis that contributes to EEC development. Cancer Res; 74(18); 5103-17. ©2014 AACR.
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.affiliation: Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Tat-San
authors.initials: TS
authors.lastname: Lau
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
authors.forename: Erling A
authors.initials: EA
authors.lastname: Hoivik
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.affiliation: Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. huating.wang@cuhk.edu.hk.
authors.forename: Huating
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C557041:MALAT1 long non-coding RNA, human; C438603:PCDH10 protein, human; D000091363:Protocadherins; D062085:RNA, Long Noncoding; D051176:beta Catenin