BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14 .

Autor:	Hillman JC; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Pugacheva EM; Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland., Barger CJ; Eppley Institute and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska., Sribenja S; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Rosario S; Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Albahrani M; Eppley Institute and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska., Truskinovsky AM; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Stablewski A; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Liu S; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Loukinov DI; Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland., Zentner GE; Department of Biology, Indiana University, Bloomington, Indiana.; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana., Lobanenkov VV; Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland., Karpf AR; Eppley Institute and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska. michael.higgins@roswellpark.org adam.karpf@unmc.edu., Higgins MJ; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York. michael.higgins@roswellpark.org adam.karpf@unmc.edu.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2019 Oct; Vol. 17 (10), pp. 2051-2062. Date of Electronic Publication: 2019 Jul 10.
DOI:	10.1158/1541-7786.MCR-19-0310
Abstrakt:	High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer-related death. We have previously shown that CTCFL (also known as BORIS , B rother o f the R egulator of I mprinted S ites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS -expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14 , a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14 . Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14 , and suggests BORIS as a potential therapeutic target in this malignancy. IMPLICATIONS: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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