Titre :

Distinct substrate specificities of human GlcNAc-6-sulfotransferases revealed by mass spectrometry-based sulfoglycomic analysis.

Auteur(s) :

Yu, Shin-Yi [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Hsiao, Cheng-Te [Auteur]
Izawa, Mineko [Auteur]
Yusa, Akiko [Auteur]
Ishida, Hiroji [Auteur]
Nakamura, Shigeo [Auteur]
Yagi, Hirokazu [Auteur]
Kannagi, Reiji [Auteur]
Khoo, Kay-Hooi [Auteur]

Titre de la revue :

Journal of biological inorganic chemistry: JBIC: a publication of the Society of Biological Inorganic Chemistry

Nom court de la revue :

J. Biol. Chem.

Numéro :

293

Pagination :

15163-15177

Date de publication :

2018-09

ISSN :

1083-351X

Mot(s)-clé(s) :

mass spectrometry (MS)
glycobiology
glycomics
analytical chemistry
colorectal cancer
GlcNAc-6-O-sulfotransferase
CHST
MECA-79
sulfoglycomics

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Sulfated glycans are known to be involved in several glycan-mediated cell adhesion and recognition pathways. Our mRNA transcript analyses on the genes involved in synthesizing GlcNAc-6-O–sulfated glycans in human colon ...
Lire la suite >Sulfated glycans are known to be involved in several glycan-mediated cell adhesion and recognition pathways. Our mRNA transcript analyses on the genes involved in synthesizing GlcNAc-6-O–sulfated glycans in human colon cancer tissues indicated that GlcNAc6ST-2 (CHST4) is preferentially expressed in cancer cells compared with nonmalignant epithelial cells among the three known major GlcNAc-6-O-sulfotransferases. On the contrary, GlcNAc6ST-3 (CHST5) was only expressed in nonmalignant epithelial cells, whereas GlcNAc6ST-1 (CHST2) was expressed equally in both cancerous and nonmalignant epithelial cells. These results suggest that 6-O-sulfated glycans that are synthesized only by GlcNAc6ST-2 may be highly colon cancer–specific, as supported by immunohistochemical staining of cancer cells using the MECA-79 antibody known to be relatively specific to the enzymatic reaction products of GlcNAc6ST-2. By more precise MS-based sulfoglycomic analyses, we sought to further infer the substrate specificities of GlcNAc6STs via a definitive mapping of various sulfo-glycotopes and O-glycan structures expressed in response to overexpression of transfected GlcNAc6STs in the SW480 colon cancer cell line. By detailed MS/MS sequencing, GlcNAc6ST-3 was shown to preferentially add sulfate onto core 2–based O-glycan structures, but it does not act on extended core 1 structures, whereas GlcNAc6ST-1 prefers core 2–based O-glycans to extended core 1 structures. In contrast, GlcNAc6ST-2 could efficiently add sulfate onto both extended core 1– and core 2–based O-glycans, leading to the production of unique sulfated extended core 1 structures such as R-GlcNAc(6-SO3−)β1-3Galβ1–4GlcNAc(6-SO3−)β1–3Galβ1–3GalNAcα, which are good candidates to be targeted as cancer-specific glycans.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Immunity, inflammation and fibrsis in auto and allo-reactivity

Date de dépôt :

2019-03-01T14:35:24Z
2024-03-08T08:49:28Z