Comparative site-specific N-glycoproteome analysis reveals aberrant N-glycosylation and gives insights into mannose-6-phosphate pathway in cancer

被引：9

作者：

Chen, Minyong ^{[1
]}

Assis, Diego M. ^{[2
]}

Benet, Matthieu ^{[1
]}

McClung, Colleen M. ^{[1
]}

Gordon, Elizabeth A. ^{[2
]}

Ghose, Shourjo ^{[2
]}

Dupard, Steven J. ^{[1
]}

Willetts, Matthew ^{[2
]}

Taron, Christopher H. ^{[1
]}

Samuelson, James C. ^{[1
]}

机构：

[1] New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA

[2] Bruker, 40 Manning Rd, Billerica, MA 01821 USA

来源：

COMMUNICATIONS BIOLOGY | 2023年 / 6卷 / 01期

关键词：

MANNOSE; PROTEINS; TUMOR; RECOGNITION; M6P/IGF2R; MARKER; BREAST; EPCAM;

D O I：

10.1038/s42003-023-04439-4

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

N-glycosylation is implicated in cancers and aberrant N-glycosylation is recognized as a hallmark of cancer. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 displays hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells. This comparative site-specific N-glycoproteome analysis provides a pool of potential N-glycosylation-related cancer biomarkers, but also gives insights into the M6P pathway in cancer. Comparative site-specific N-glycoproteome analysis of tumorigenic and non-tumorigenic colon cancer cells provides a pool of potential N-glycosylation related cancer biomarkers and insights into the mannose-6-phosphate pathway in cancer.

引用

页数：17