Dataset Information

N-glycoproteins have a major role in MGL binding to colorectal cancer cell lines

ABSTRACT: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL binding glycoproteins in two high MGL binding CRC cells lines, HCT116 and HT29. We investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Yassene Mohammed

LAB HEAD: Paul J. Hensbergen

PROVIDER: PXD020344 | Pride | 2020-08-10

REPOSITORIES: Pride

ACCESS DATA

Publications

<i>N</i>-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity.

Pirro Martina M Mohammed Yassene Y van Vliet Sandra J SJ Rombouts Yoann Y Sciacca Agnese A de Ru Arnoud H AH Janssen George M C GMC Tjokrodirijo Rayman T N RTN Wuhrer Manfred M van Veelen Peter A PA Hensbergen Paul J PJ

International journal of molecular sciences 20200801 15

Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. W ...[more]

PMID: 32752259

Similar Datasets

Project description:Colorectal cancer (CRC) is one of the most lethal cancers when it progresses to the advanced/metastatic stage. Treatment options for refractory metastatic colorectal cancer (mCRC) are limited. Therefore, there is an urgent need to develop effective treatment methods for metastatic colorectal cancer. In this study, we screened a library of small molecules for inhibitors of CRC recurrence using CRC cell lines and patient-derived organoids (PDOs) from metastatic, heavily pretreated CRC. The in vivo efficacy of LS-1-2 was evaluated in the HCT116 and the resistant HCT8 cell lines, patient-derived xenografts(PDXs) including refractory mCRC, and a liver metastasis mouse model. Biotin pull-down and liquid chromatography tandem-mass spectrometry (LC-MS/MS) were performed to identify proteins that interact with LS-1-2. The genome-wide gene expression and quantitative phosphoproteomic analyses were performed to determine the signaling pathway involved in LS-1-2. Molecular docking, molecular dynamics analysis and cellular thermal shift assays were used to predict and validate the binding sites of LS-1-2 on non-muscle Myosin IIA (NMHC IIA). Our results showed that LS-1-2 exhibited broad antiproliferative effects on a series of CRC cell lines and PDOs. The in vivo anti-tumor efficacy of LS-1-2 was demonstrated across cell line- and patient-derived xenografts and in the liver metastatic CRC model. NMHC IIA was identified as a direct target of LS-1-2, and LS-1-2 competitively inhibited the phosphorylation of NMHC IIA at S1943 and S1714 by CK2. NMHC IIA phosphorylation promoted CRC cell proliferation and invasion, which was reduced by LS-1-2. NMHC IIA phosphorylation-mediated YAP activity induced activation of AKT and inactivation of FOXO3a and was suppressed by LS-1-2. In conclusion, our findings suggest that NMHC IIA phosphorylation can be used as a potential molecular target in CRC metastasis, and that targeting NMHC IIA phosphorylation by LS-1-2 may be a promising strategy for the treatment and prevention of CRC metastasis.

Dataset Information

N-glycoproteins have a major role in MGL binding to colorectal cancer cell lines

Publications

<i>N</i>-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure