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 : Sussex Research Online

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Morgan, R G, Molnár, E, Jones, R F, Collard, T J, Lane, J D, Greenhough, A, Paraskeva, C and 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). pp. 714-719. ISSN 1532-1827

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Official URL: http://dx.doi.org/10.1038/bjc.2015.4

Abstract

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.

Item Type:	Article
Keywords:	LGR5 Glycosylation Colorectal Cancer Stem Cell Nutrient Stress Microenvironment
Schools and Departments:	School of Life Sciences > Biochemistry
Depositing User:	Rhys Morgan
Date Deposited:	10 May 2018 13:54
Last Modified:	02 Jul 2019 15:47
URI:	http://sro.sussex.ac.uk/id/eprint/75695

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