MUC1 O-glycosylation contributes to anoikis resistance in epithelial cancer cells



Piyush, T, Rhodes, JM ORCID: 0000-0002-1302-260X and Yu, LG ORCID: 0000-0001-9641-3712
(2017) MUC1 O-glycosylation contributes to anoikis resistance in epithelial cancer cells. Cell Death Discovery, 3.

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Abstract

Anoikis is a fundamental cellular process for maintaining tissue homeostasis. Resistance to anoikis is a hallmark of oncogenic epithelial–mesenchymal transition and is a pre-requisite for metastasis. Previous studies have revealed that the heavily glycosylated mucin protein MUC1, which is overexpressed in all types of epithelial cancer cells, prevents anoikis initiation in response to loss of adhesion. This effect of MUC1 is largely attributed to its extracellular domain that provides cell surface anoikis-initiating molecules with a ‘homing’ microenvironment. The present study investigated the influence of O-glycosylation on MUC1 extracellular domain on MUC1-mediated cell resistance to anoikis. It shows that stable suppression of the Core 1Gal-transferase (C1GT) by shRNA substantially reduces O-glycosylation in MUC1-positively transfected human colon cancer HCT116 cells and in high MUC1-expressing SW620 cells. Suppression of C1GT significantly increased anoikis of the MUC1-positive, but not MUC1-negative, cells in response to suspended culture. This effect was shown to be associated with increased ligand accessibility to cell surface anoikis-initiating molecules such as E-cadherin, integrinβ1 and Fas. These results indicate that the extensive O-glycosylation on MUC1 extracellular domain contributes to MUC1-mediated cell resistance to anoikis by facilitating MUC1-mediated prohibition of activation of the cell surface anoikis-initiating molecules in response to loss of cell adhesion. This provides insight into the molecular mechanism of anoikis regulation and highlights the importance of cellular glycosylation in cancer progression and metastasis.

Item Type: Article
Uncontrolled Keywords: apoptosis, glycobiology
Depositing User: Symplectic Admin
Date Deposited: 17 Jul 2017 08:31
Last Modified: 25 Jan 2022 18:14
DOI: 10.1038/cddiscovery.2017.44
Open Access URL: https://www.nature.com/articles/cddiscovery201744
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3008509

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