"2018-01-23" . . . . "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\u2013proline 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 oestrogen receptor (ER)+/human epidermal growth factor receptor (HER2)\u2013 high proliferation class (Luminal B) compared with ER+/HER2\u2013 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\u2013proline regulatory axis genes revealed significant associations with molecular subtypes of BC and patient outcome independent of standard clinicopathological parameters (P=0.012). High protein expression of the glutamine\u2013proline enzymes were all associated with high MYC protein in Luminal B tumours only (P<0.001). Conclusions: We provide comprehensive clinical data indicating that the glutamine\u2013proline regulatory axis plays an important role in the aggressive subclass of luminal BC and is therefore a potential therapeutic target."^^ . . . . . . . . "118" . . . . . . . . . "2" . . . . . . . . . . . . . . . . "MYC regulation of glutamine--proline regulatory axis is key in luminal B breast cancer"^^ . . .