Author
Listed:
- Emmanuel Dornier
(Garscube Estate)
- Nicolas Rabas
(Garscube Estate)
- Louise Mitchell
(Garscube Estate)
- David Novo
(Garscube Estate)
- Sandeep Dhayade
(Garscube Estate)
- Sergi Marco
(Garscube Estate)
- Gillian Mackay
(Garscube Estate)
- David Sumpton
(Garscube Estate)
- Maria Pallares
(Garscube Estate)
- Colin Nixon
(Garscube Estate)
- Karen Blyth
(Garscube Estate)
- Iain R. Macpherson
(Garscube Estate
University of Glasgow)
- Elena Rainero
(Garscube Estate
The University of Sheffield, Western Bank)
- Jim C. Norman
(Garscube Estate
University of Glasgow)
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.
Suggested Citation
Emmanuel Dornier & Nicolas Rabas & Louise Mitchell & David Novo & Sandeep Dhayade & Sergi Marco & Gillian Mackay & David Sumpton & Maria Pallares & Colin Nixon & Karen Blyth & Iain R. Macpherson & Ele, 2017.
"Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells,"
Nature Communications, Nature, vol. 8(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02101-2
DOI: 10.1038/s41467-017-02101-2
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02101-2. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.