当前位置： SCI文献检索 > BRITISH JOURNAL OF CANCER期刊下所有文献 > 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.

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.

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.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Morgan RG,Molnár E,Jones RF,Collard TJ,Lane JD,Greenhough A,Paraskeva C,Williams AC

doi

10.1038/bjc.2015.4

subject

Has Abstract

pub_date

2015-02-17 00:00:00

pages

714-9

issue

4

eissn

0007-0920

issn

1532-1827

pii

bjc20154

journal_volume

112

pub_type

杂志文章

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