Dornier, E. et al. (2017) Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells. Nature Communications, 8, 2255. (doi: 10.1038/s41467-017-02101-2) (PMID:29269878) (PMCID:PMC5740148)
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Abstract
The role of glutaminolysis in providing metabolites to support tumour growth is well-established, but the involvement of glutamine metabolism in invasive processes is yet to be elucidated. Here we show that normal mammary epithelial cells consume glutamine, but do not secrete glutamate. Indeed, low levels of extracellular glutamate are necessary to maintain epithelial homoeostasis, and provision of glutamate drives disruption of epithelial morphology and promotes key characteristics of the invasive phenotype such as lumen-filling and basement membrane disruption. By contrast, primary cultures of invasive breast cancer cells convert glutamine to glutamate which is released from the cell through the system Xc- antiporter to activate a metabotropic glutamate receptor. This contributes to the intrinsic aggressiveness of these cells by upregulating Rab27-dependent recycling of the transmembrane matrix metalloprotease, MT1-MMP to promote invasive behaviour leading to basement membrane disruption. These data indicate that acquisition of the ability to release glutamate is a key watershed in disease aggressiveness.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Pallares Masmitja, Ms Maria and Blyth, Professor Karen and Sumpton, Mr David and MacPherson, Professor Iain and Mackay, Dr Gillian and Norman, Professor James and Fontinha da Silva Novo, David and Mitchell, Mrs Louise and Rabas, Nicolas and Rainero, Ms Elena and Nixon, Mr Colin and Dornier, Mr Emmanuel Greg |
Authors: | Dornier, E., Rabas, N., Mitchell, L., Novo, D., Dhayade, S., Marco, S., Mackay, G., Sumpton, D., Pallares, M., Nixon, C., Blyth, K., MacPherson, I. R., Rainero, E., and Norman, J. C. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Nature Communications |
Publisher: | Nature Research |
ISSN: | 2041-1723 |
ISSN (Online): | 2041-1723 |
Copyright Holders: | Copyright © 2017 The Authors |
First Published: | First published in Nature Communications 8: 2255 |
Publisher Policy: | Reproduced under a Creative Commons License |
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