Madeleine L. Craze
MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer
Craze, Madeleine L.; Cheung, Hayley; Jewa, Natasha; Coimbra, Nuno D.M.; Soria, Daniele; El-Ansari, Rokaya; Aleskandarany, Mohammed A.; Cheng, Kiu Wai; Diez-Rodriguez, Maria; Nolan, Christopher C.; Ellis, Ian O.; Rakha, Emad; Green, Andrew R.
Authors
Hayley Cheung
Natasha Jewa
Nuno D.M. Coimbra
Daniele Soria
Rokaya El-Ansari
Mohammed A. Aleskandarany
Kiu Wai Cheng
Maria Diez-Rodriguez
Christopher C. Nolan
Ian O. Ellis
Professor EMAD RAKHA Emad.Rakha@nottingham.ac.uk
PROFESSOR OF BREAST CANCER PATHOLOGY
Dr Andy Green ANDREW.GREEN@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR
Abstract
Background: Altered cellular metabolism is a hallmark of cancer and some are reliant on Glutamine for sustained proliferation and survival. We hypothesise that the Glutamine-Proline regulatory axis has a key role in Breast cancer (BC) in the highly proliferative classes.
Methods: Glutaminase (GLS), pyrroline-5-carboxylate synthetase (ALDH18A1) and pyrroline-5-carboxylate reductase 1 (PYCR1) were assessed at DNA/mRNA/protein levels in large well-characterised cohorts.
Results: Gain of PYCR1 copy number and high PYCR1 mRNA was associated with luminal B tumours. High ALDH18A1 and high GLS protein expression was observed in the ER+/HER2- high proliferation class (Luminal B) compared with ER+/HER2- low proliferation class (Luminal A) (p=0.030 and p=0.022 respectively), however this was not observed with mRNA. Cluster analysis of the Glutamine-Proline regulatory axis genes revealed significant associations with molecular subtypes of breast cancer and patient outcome independent of standard clinicopathological parameters (p=0.012). High protein expression of the Glutamine-Proline enzymes were all associated with high MYC protein in Luminal B tumours only (p<0.001).
Conclusion: We provide comprehensive clinical data indicating that the Glutamine-Proline regulatory axis plays an important role in the aggressive subclass of luminal BC and is therefore a potential therapeutic target.
Citation
Craze, M. L., Cheung, H., Jewa, N., Coimbra, N. D., Soria, D., El-Ansari, R., Aleskandarany, M. A., Cheng, K. W., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., Rakha, E., & Green, A. R. (in press). MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer. British Journal of Cancer, https://doi.org/10.1038/bjc.2017.387
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 4, 2017 |
Online Publication Date | Nov 23, 2017 |
Deposit Date | Oct 24, 2017 |
Publicly Available Date | Nov 23, 2017 |
Journal | British Journal of Cancer |
Print ISSN | 0007-0920 |
Electronic ISSN | 1532-1827 |
Publisher | Cancer Research UK |
Peer Reviewed | Peer Reviewed |
DOI | https://doi.org/10.1038/bjc.2017.387 |
Keywords | metabolism, breast cancer, prognosis, Luminal B, glutamine, proline |
Public URL | https://nottingham-repository.worktribe.com/output/896557 |
Publisher URL | https://www.nature.com/articles/bjc2017387 |
Contract Date | Oct 24, 2017 |
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