Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: Implications for targeting cancer stem cells

Williams, A. C.; Paraskeva, C.; Greenhough, A.; Lane, J. D.; Collard, T. J.; Jones, R. F.; Moln�r, E.; Morgan, R. G.; Morgan, Rhys G; Molnar, Elek; Jones, Rosie F; Collard, Tracey J; Lane, Jon D; Greenhough, Alexander; Paraskeva, Chris; Williams, Ann C

Abstract

© 2015 Cancer Research UK. Background:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein.Methods:Nutrient stress was induced through glucose starvation. Glycosylation status was assessed using endoglycosidase or tunicamycin treatment. Flow cytometry and confocal microscopy were used to assess subcellular distribution of LGR5.Results:Glucose deprivation altered the glycosylation status of LGR5 resulting in reduced protein stability and cell surface expression. Furthermore, inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced localisation in the cis-Golgi network.Conclusions:Nutrient stress within a tumour microenvironment has the capacity to alter LGR5 protein stability and membrane localisation through modulation of LGR5 glycosylation status. As LGR5 surface localisation is required for enhanced Wnt signalling, this is the first report to show a mechanism by which the microenvironment could affect LGR5 function.

Citation

Williams, A. C., Paraskeva, C., Greenhough, A., Lane, J. D., Collard, T. J., Jones, R. F., …Williams, A. C. (2015). Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: Implications for targeting cancer stem cells. British Journal of Cancer, 112(4), 714-719. https://doi.org/10.1038/bjc.2015.4

• Journal Article Type: Article
• Acceptance Date: Dec 22, 2014
• Online Publication Date: Jan 22, 2015
• Publication Date: Feb 17, 2015
• Deposit Date: Feb 12, 2019
• Publicly Available Date: Feb 14, 2019
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Springer Nature [academic journals on nature.com]
• Peer Reviewed: Peer Reviewed
• Volume: 112
• Issue: 4
• Pages: 714-719
• DOI: https://doi.org/10.1038/bjc.2015.4
• Public URL: https://uwe-repository.worktribe.com/output/838435
• Publisher URL: https://doi.org/10.1038/bjc.2015.4