title: All-trans-retinoic acid modulates ICAM-1 N-glycan composition by influencing GnT-III levels and inhibits cell adhesion and trans-endothelial migration.
abstract: Changes in the expression of glycosyltransferases directly influence the oligosaccharide structures and conformations of cell surface glycoproteins and consequently cellular phenotype transitions and biological behaviors. In the present study, we show that all-trans-retinoic acid (ATRA) modulates the N-glycan composition of intercellular adhesion molecule-1 (ICAM-1) by manipulating the expression of two N-acetylglucosaminyltransferases, GnT-III and GnT-V, via the ERK signaling pathway. Exposure of various cells to ATRA caused a remarkable gel mobility down-shift of ICAM-1. Treatment with PNGase F confirmed that the reduction of the ICAM-1 molecular mass is attributed to the decreased complexity of N-glycans. We noticed that the expression of the mRNA encoding GnT-III, which stops branching, was significantly enhanced following ATRA exposure. In contrast, the level of the mRNA encoding GnT-V, which promotes branching, was reduced following ATRA exposure. Silencing of GnT-III prevented the molecular mass shift of ICAM-1. Moreover, ATRA induction greatly inhibited the adhesion of SW480 and U937 cells to the HUVEC monolayer, whereas knock-down of GnT-III expression effectively restored cell adhesion function. Treatment with ATRA also dramatically reduced the trans-endothelial migration of U937 cells. These data indicate that the alteration of ICAM-1 N-glycan composition by ATRA-induced GnT-III activities hindered cell adhesion and cell migration functions simultaneously, pinpointing a unique regulatory role of specific glycosyltransferases in the biological behaviors of tumor cells and a novel function of ATRA in the modulation of ICAM-1 N-glycan composition.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing, PR China.
authors.forename: Changguo
authors.initials: C
authors.lastname: Chen
authors.forename: Dekun
authors.initials: D
authors.lastname: Diao
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Meiru
authors.initials: M
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Lu
authors.initials: L
authors.lastname: Qian
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D011134:Polysaccharides; D018799:Intercellular Adhesion Molecule-1; D014212:Tretinoin; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase