BORIS expression in ovarian cancer precursor cells alters the CTCF cistrome and enhances invasiveness through GALNT14

Joanna C. Hillman, Elena M. Pugacheva, Carter J. Barger, Sirinapa Sribenja, Spencer Rosario, Mustafa Albahrani, Alexander M. Truskinovsky, Aimee Stablewski, Song Liu, Dmitri I. Loukinov, Gabriel E. Zentner, Victor V. Lobanenkov, Adam R. Karpf, Michael J. Higgins

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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, Brother of the Regulator of Imprinted Sites) 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. BORISexpressing 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.

Original languageEnglish (US)
Pages (from-to)2051-2062
Number of pages12
JournalMolecular Cancer Research
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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