MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer
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),...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Cancer Research UK
2017
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| Online Access: | https://eprints.nottingham.ac.uk/47502/ |
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| author | 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. |
| author_facet | 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. |
| author_sort | Craze, Madeleine L. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:05:51Z |
| format | Article |
| id | nottingham-47502 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:05:51Z |
| publishDate | 2017 |
| publisher | Cancer Research UK |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-475022024-08-15T15:25:18Z https://eprints.nottingham.ac.uk/47502/ 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. 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. Cancer Research UK 2017-11-23 Article PeerReviewed 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 and Green, Andrew R. (2017) MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer. British Journal of Cancer . ISSN 1532-1827 metabolism breast cancer prognosis Luminal B glutamine proline https://www.nature.com/articles/bjc2017387 doi:10.1038/bjc.2017.387 doi:10.1038/bjc.2017.387 |
| spellingShingle | metabolism breast cancer prognosis Luminal B glutamine proline 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. MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title | MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title_full | MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title_fullStr | MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title_full_unstemmed | MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title_short | MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer |
| title_sort | myc regulation of glutamine-proline regulatory axis is key in luminal b breast cancer |
| topic | metabolism breast cancer prognosis Luminal B glutamine proline |
| url | https://eprints.nottingham.ac.uk/47502/ https://eprints.nottingham.ac.uk/47502/ https://eprints.nottingham.ac.uk/47502/ |