Projects per year
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 714-719 |
| Number of pages | 6 |
| Journal | British Journal of Cancer |
| Volume | 112 |
| Issue number | 4 |
| Early online date | 22 Jan 2015 |
| DOIs | |
| Publication status | Published - 17 Feb 2015 |
Keywords
- LGR5
- glycosylation
- colorectal cancer
- stem cell
- nutrient stress
- microenvironment
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Dive into the research topics of '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'. Together they form a unique fingerprint.Projects
- 1 Finished
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Development of biotin-tagged affinity ligands and fluorophore-conjugated probes for the study of native kainate receptors
1/03/13 → 1/03/16
Project: Research
Equipment
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Wolfson Bioimaging Facility
Mark Jepson (Manager)
Faculty of Life SciencesFacility/equipment: Facility
Profiles
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Professor Jon D Lane
- School of Biochemistry - Professor of Cell Biology
- Fundamental Bioscience
- Cancer
- Dynamic Cell Biology
Person: Academic , Member
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Professor Ann C Williams
- Fundamental Bioscience
- School of Cellular and Molecular Medicine - Professor of Experimental Oncology
- Cancer
- Dynamic Cell Biology
Person: Academic , Member