title: Silencing the Nucleocytoplasmic O-GlcNAc Transferase Reduces Proliferation, Adhesion, and Migration of Cancer and Fetal Human Colon Cell Lines.
abstract: The post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is regulated by a unique couple of enzymes. O-GlcNAc transferase (OGT) transfers the GlcNAc residue from UDP-GlcNAc, the final product of the hexosamine biosynthetic pathway (HBP), whereas O-GlcNAcase (OGA) removes it. This study and others show that OGT and O-GlcNAcylation levels are increased in cancer cell lines. In that context, we studied the effect of OGT silencing in the colon cancer cell lines HT29 and HCT116 and the primary colon cell line CCD841CoN. Herein, we report that OGT silencing diminished proliferation, in vitro cell survival and adhesion of primary and cancer cell lines. SiOGT dramatically decreased HT29 and CCD841CoN migration, CCD841CoN harboring high capabilities of migration in Boyden chamber system when compared to HT29 and HCT116. The expression levels of actin and tubulin were unaffected by OGT knockdown but siOGT seemed to disorganize microfilament, microtubule, and vinculin networks in CCD841CoN. While cancer cell lines harbor higher levels of OGT and O-GlcNAcylation to fulfill their proliferative and migratory properties, in agreement with their higher consumption of HBP main substrates glucose and glutamine, our data demonstrate that OGT expression is not only necessary for the biological properties of cancer cell lines but also for normal cells.
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille , Lille , France.
authors.forename: Agata
authors.initials: A
authors.lastname: Steenackers
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille, Lille, France; Laboratory of Cellular and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD, USA.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Olivier-Van Stichelen
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille , Lille , France.
authors.forename: Steffi F
authors.initials: SF
authors.lastname: Baldini
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille, Lille, France; CNRS, UMR 8161, M3T, Mechanisms of Tumorigenesis and Targeted Therapies, «Institut de Biologie de Lille», Pasteur Institute of Lille, FRABio FR 3688, University of Lille, Lille Cedex, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dehennaut
authors.affiliation: U908, CPAC, Cell Plasticity and Cancer, INSERM, University of Lille , Lille , France.
authors.forename: Robert-Alain
authors.initials: RA
authors.lastname: Toillon
authors.affiliation: U908, CPAC, Cell Plasticity and Cancer, INSERM, University of Lille , Lille , France.
authors.forename: Xuefen
authors.initials: X
authors.lastname: Le Bourhis
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille , Lille , France.
authors.forename: Ikram
authors.initials: I
authors.lastname: El Yazidi-Belkoura
authors.affiliation: CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, FRABio FR 3688, University of Lille , Lille , France.
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre
keywords: O-GlcNAcylation; O-linked N-acetylglucosamine transferase; colon cell lines; colorectal cancer; siRNA