Imperial College London
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ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sierra:2018:10.1038/s41586-018-0729-3,
author = {Sierra, Gonzalez P and OPrey, J and Cardaci, S and Barthet, V and Sakamaki, J-I and Beaumatin, F and Roseweir, A and Gay, D and Mackay, G and Malviya, G and Kania, E and Ritchie, S and Baudot, A and Zunino, B and Mrowinska, A and Nixon, C and Ennis, D and Hoyle, A and Millan, D and McNeish, I and Sansom, O and Edwards, J and Ryan, K},
doi = {10.1038/s41586-018-0729-3},
journal = {Nature},
pages = {719--723},
title = {Mannose impairs tumour growth and enhances chemotherapy},
url = {http://dx.doi.org/10.1038/s41586-018-0729-3},
volume = {563},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - It is now well established that tumours undergo changes in cellular metabolism1. As this can reveal tumour cell vulnerabilities and because many tumours exhibit enhanced glucose uptake2, we have been interested in how tumour cells respond to different forms of sugar. Here we report that the monosaccharide mannose causes growth retardation in several tumour types in vitro, and enhances cell death in response to major forms of chemotherapy. We then show that these effects also occur in vivo in mice following the oral administration of mannose, without significantly affecting the weight and health of the animals. Mechanistically, mannose is taken up by the same transporter(s) as glucose3 but accumulates as mannose-6-phosphate in cells, and this impairs the further metabolism of glucose in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway and glycan synthesis. As a result, the administration of mannose in combination with conventional chemotherapy affects levels of anti-apoptotic proteins of the Bcl-2 family, leading to sensitization to cell death. Finally we show that susceptibility to mannose is dependent on the levels of phosphomannose isomerase (PMI). Cells with low levels of PMI are sensitive to mannose, whereas cells with high levels are resistant, but can be made sensitive by RNA-interference-mediated depletion of the enzyme. In addition, we use tissue microarrays to show that PMI levels also vary greatly between different patients and different tumour types, indicating that PMI levels could be used as a biomarker to direct the successful administration of mannose. We consider that the administration of mannose could be a simple, safe and selective therapy in the treatment of cancer, and could be applicable to multiple tumour types.
AU  - Sierra,Gonzalez P
AU  - OPrey,J
AU  - Cardaci,S
AU  - Barthet,V
AU  - Sakamaki,J-I
AU  - Beaumatin,F
AU  - Roseweir,A
AU  - Gay,D
AU  - Mackay,G
AU  - Malviya,G
AU  - Kania,E
AU  - Ritchie,S
AU  - Baudot,A
AU  - Zunino,B
AU  - Mrowinska,A
AU  - Nixon,C
AU  - Ennis,D
AU  - Hoyle,A
AU  - Millan,D
AU  - McNeish,I
AU  - Sansom,O
AU  - Edwards,J
AU  - Ryan,K
DO  - 10.1038/s41586-018-0729-3
EP  - 723
PY  - 2018///
SN  - 0028-0836
SP  - 719
TI  - Mannose impairs tumour growth and enhances chemotherapy
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-018-0729-3
UR  - https://www.nature.com/articles/s41586-018-0729-3
UR  - http://hdl.handle.net/10044/1/65247
VL  - 563
ER  -
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