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Glutamine Metabolism in Cancer
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Glutamine Metabolism in Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 1664

Special Issue Editor

Dr. Andrew R. Green

E-Mail Website
Guest Editor
Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
Interests: breast cancer; pathology; metabolism; prognosis; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer, a major global health concern, exhibits significant clinical and biological heterogeneity, highlighting the need for personalised treatment approaches. Metabolic reprogramming has been recognised as a hallmark of cancer, and many aggressive cancer cells can become “glutamine-addicted”, relying heavily on this amino acid for rapid growth. Glutamine is used to replenish the tricarboxylic-acid (TCA) cycle and supplies carbon and nitrogen for the synthesis of nucleotides, amino acids, and glutathione. Its utilisation, via reductive carboxylation, is necessary for sustained proliferation/survival and is linked with resistance to certain drugs.

With a renewed interest in “oncometabolism”, the glutaminolysis pathway and cellular transport of glutamine via solute carriers are increasingly focused upon, with the aim of improving therapeutic efficacy and reducing resistance. Exploring this vital metabolic axis will allow us to gain valuable insights into cancer heterogeneity and pave the way for personalised treatment approaches for patients. This Special Issue therefore welcomes original research regarding all aspects of glutamine metabolism in cancer, including, but not limited to, cancer progression, redox homeostatsis, apopotosis, ferroptosis, the immune response, and the role of the tumour microenvironment.

Dr. Andrew R. Green
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glutamine metabolism
  • cancer
  • oncometabolism
  • cancer metabolism
  • metabolic reprogramming
  • personalised medicine
  • therapeutic resistance
  • drug targets

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Published Papers (1 paper)

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Research

19 pages, 5775 KiB  
Article
Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer
by Busra Erkan, Skye MacIntyre, Charlotte Brown, Ali Fakroun, Ayat G. Lashen, Nigel P. Mongan, Ian O. Ellis, Emad A. Rakha and Andrew R. Green
Int. J. Mol. Sci. 2024, 25(21), 11572; https://doi.org/10.3390/ijms252111572 - 28 Oct 2024
Viewed by 1420
Abstract
Breast cancer (BC), which remains the most prevalent malignancy among women, is characterised by significant heterogeneity across its molecular subtypes. Oestrogen receptor-positive (ER+) (luminal) BC represents approximately 75% of cases, and despite advancements in treatment there remains around a 40% recurrence rate. Cellular [...] Read more.
Breast cancer (BC), which remains the most prevalent malignancy among women, is characterised by significant heterogeneity across its molecular subtypes. Oestrogen receptor-positive (ER+) (luminal) BC represents approximately 75% of cases, and despite advancements in treatment there remains around a 40% recurrence rate. Cellular uptake of glutamine is conducted by solute carriers (SLCs), which are significantly associated with outcome in luminal BC. In this study, differential gene expression analysis was carried out using The Cancer Genome Atlas BC dataset. This identified hydroxyacid oxidase 1 (HAO1) as significantly overexpressed in luminal BC with a high expression of SLCs. Extended analysis in the METABRIC (n = 1980) and Breast Cancer Gene-Expression Miner (n = 4421) transcriptomic databases and the Nottingham (n = 952) BC tissue cohort showed a varied survival outcome for HAO1 expression at the genomic, transcriptomic, and proteomic levels. HAO1 copy number (CN) gain (p = 0.002) and high HAO1 protein expression (p = 0.019) were associated with poor prognosis in luminal BC, whereas high HAO1 mRNA expression correlated with better survival outcomes (p = 0.023) suggesting a complex regulatory mechanism affecting HAO1 at different biological levels. Importantly, in luminal BC patients treated with endocrine therapy, high protein expression of HAO1 predicted shorter distant-metastasis free survival (p = 0.042). The knockdown of SLC1A5 and SLC7A5 significantly reduced HAO1 expression in MCF-7 and ZR-751 BC cell lines. Protein analysis confirmed significant associations between HAO1 and SLC7A5 and SLC1A5, emphasising a potential role for the enzyme in glutamine metabolism and its potential as a therapeutic target. This study underscores the prognostic significance of HAO1 in luminal BC and its relationship with patient outcomes. Full article
(This article belongs to the Special Issue Glutamine Metabolism in Cancer)
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