University of Oulu

Khosrowabadi, E., Wenta, T., Keskitalo, S., Manninen, A., & Kellokumpu, S. (2022). Altered glycosylation of several metastasis-associated glycoproteins with terminal GalNAc defines the highly invasive cancer cell phenotype. Oncotarget, 13(1), 73–89.

Altered glycosylation of several metastasis-associated glycoproteins with terminal GalNAc defines the highly invasive cancer cell phenotype

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Author: Khosrowabadi, Elham1; Wenta, Tomasz1; Keskitalo, Salla2;
Organizations: 1University of Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu, Finland
2Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 8.1 MB)
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Language: English
Published: Impact Journals, 2022
Publish Date: 2022-07-04


Several distinct metastasis-associated glycosylation changes have been shown to promote cancer cell invasion and metastasis, the main cause of death of cancer patients. However, it is unclear whether their presence reflects cell- or tissue-specific variations for metastasis, or species needed to drive different phases of the metastatic cascade. To address this issue from a different perspective, we investigated here whether different cancer cell lines share any glycotopes that are common and important for their invasive phenotype. By using lectin microarray glycan profiling and an established myoma tissue-based 3D invasion assay, we identified a single glycotope recognized by Helix Pomatia agglutinin (HPA), whose expression level in different cancer cells correlated significantly with their invasive potential. Lectin pull-down assay and LC-MS/MS analysis in highly- (A431 and SW-48) and poorly invasive (HepG2 and RCC4) cancer cells revealed ~85 glycoproteins of which several metastasis-promoting members of the integrin family of cell adhesion receptors, the epidermal growth factor receptor (EGFR) and the matrix metalloproteinase-14 (MMP-14) were among the abundant ones. Moreover, we showed that the level of the GalNAc glycotope in MMP-14, EGFR, αV-, β1- and β4 integrin in highly and poorly invasive cancer cells correlated positively with their invasive potential. Collectively, our findings suggest that altered glycosylation of several metastasis-associated glycoproteins with terminal GalNAc drives the highly invasive cancer cell phenotype.

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Series: Oncotarget
ISSN: 1949-2553
ISSN-E: 1949-2553
ISSN-L: 1949-2553
Volume: 13
Pages: 73 - 89
DOI: 10.18632/oncotarget.28167
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3122 Cancers
Funding: We acknowledge the University of Oulu Graduate School, the Finnish National Agency for Education (CIMO), the Thelma Mäkikyrö Foundation, and the Academy of Finland for funding.
Copyright information: © 2022 Khosrowabadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.