Nitrogen Metabolism in Cancer and Immunity

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2020 Apr 18

PMID 32302552

Citations 53

Authors

Kiran Kurmi

Marcia C Haigis

Affiliations

Soon will be listed here.

Abstract

As one of the fundamental requirements for cell growth and proliferation, nitrogen acquisition and utilization must be tightly regulated. Nitrogen can be generated from amino acids (AAs) and utilized for biosynthetic processes through transamination and deamination reactions. Importantly, limitations of nitrogen availability in cells can disrupt the synthesis of proteins, nucleic acids, and other important nitrogen-containing compounds. Rewiring cellular metabolism to support anabolic processes is a feature common to both cancer and proliferating immune cells. In this review, we discuss how nitrogen is utilized in biosynthetic pathways and highlight different metabolic and oncogenic programs that alter the flow of nitrogen to sustain biomass production and growth, an important emerging feature of cancer and immune cell proliferation.

Citing Articles

Advances in 16S rRNA-Based Microbial Biomarkers for Gastric Cancer Diagnosis and Prognosis.

Wang Y, Qiu X, Chu A, Chen J, Wang L, Sun X Microb Biotechnol. 2025; 18(2):e70115.

PMID: 39992270 PMC: 11849407. DOI: 10.1111/1751-7915.70115.

Integrative pan-cancer genomic analysis highlights mitochondrial protein p32 as a potential therapeutic target in Myc-driven tumorigenesis.

Bi Q, Nie J, Wu Q, Sun L, Zhu S, Bai J Med Oncol. 2025; 42(3):60.

PMID: 39891862 DOI: 10.1007/s12032-025-02604-9.

Citrate: a key signalling molecule and therapeutic target for bone remodeling disorder.

Liu Q, Xue Y, Guo J, Tao L, Zhu Y Front Endocrinol (Lausanne). 2025; 15:1512398.

PMID: 39886032 PMC: 11779597. DOI: 10.3389/fendo.2024.1512398.

MicroRNAs and their role in breast cancer metabolism (Review).

Lee W, Yeo B, Mahmud R, Tan G, Wahid M, Cheah Y Int J Oncol. 2024; 66(1).

PMID: 39635852 PMC: 11684793. DOI: 10.3892/ijo.2024.5713.

Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism.

Baytas O, Davidson S, Kauer J, Morrow E Mol Brain. 2024; 17(1):87.

PMID: 39604975 PMC: 11600823. DOI: 10.1186/s13041-024-01154-x.

References

van Geldermalsen M, Wang Q, Nagarajah R, Marshall A, Thoeng A, Gao D . ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene. 2015; 35(24):3201-8. PMC: 4914826. DOI: 10.1038/onc.2015.381. View

Muir A, Danai L, Gui D, Waingarten C, Lewis C, Vander Heiden M . Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. Elife. 2017; 6. PMC: 5589418. DOI: 10.7554/eLife.27713. View

Adeva M, Souto G, Blanco N, Donapetry C . Ammonium metabolism in humans. Metabolism. 2012; 61(11):1495-511. DOI: 10.1016/j.metabol.2012.07.007. View

Fultang L, Vardon A, De Santo C, Mussai F . Molecular basis and current strategies of therapeutic arginine depletion for cancer. Int J Cancer. 2016; 139(3):501-9. DOI: 10.1002/ijc.30051. View

Elorza A, Soro-Arnaiz I, Melendez-Rodriguez F, Rodriguez-Vaello V, Marsboom G, de Carcer G . HIF2α acts as an mTORC1 activator through the amino acid carrier SLC7A5. Mol Cell. 2012; 48(5):681-91. DOI: 10.1016/j.molcel.2012.09.017. View

Maddocks O, Berkers C, Mason S, Zheng L, Blyth K, Gottlieb E . Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2012; 493(7433):542-6. PMC: 6485472. DOI: 10.1038/nature11743. View

Finicle B, Jayashankar V, Edinger A . Nutrient scavenging in cancer. Nat Rev Cancer. 2018; 18(10):619-633. DOI: 10.1038/s41568-018-0048-x. View

Wyant G, Abu-Remaileh M, Wolfson R, Chen W, Freinkman E, Danai L . mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. Cell. 2017; 171(3):642-654.e12. PMC: 5704964. DOI: 10.1016/j.cell.2017.09.046. View

Ye J, Kumanova M, Hart L, Sloane K, Zhang H, De Panis D . The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J. 2010; 29(12):2082-96. PMC: 2892366. DOI: 10.1038/emboj.2010.81. View

10.

Timmerman L, Holton T, Yuneva M, Louie R, Padro M, Daemen A . Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013; 24(4):450-65. PMC: 3931310. DOI: 10.1016/j.ccr.2013.08.020. View

11.

Geiger R, Rieckmann J, Wolf T, Basso C, Feng Y, Fuhrer T . L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell. 2016; 167(3):829-842.e13. PMC: 5075284. DOI: 10.1016/j.cell.2016.09.031. View

12.

Romero R, Sayin V, Davidson S, Bauer M, Singh S, LeBoeuf S . Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med. 2017; 23(11):1362-1368. PMC: 5677540. DOI: 10.1038/nm.4407. View

13.

Biancur D, Paulo J, Malachowska B, Del Rey M, Sousa C, Wang X . Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism. Nat Commun. 2017; 8:15965. PMC: 5500878. DOI: 10.1038/ncomms15965. View

14.

Jin L, Chun J, Pan C, Kumar A, Zhang G, Ha Y . The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer. Mol Cell. 2017; 69(1):87-99.e7. PMC: 5777230. DOI: 10.1016/j.molcel.2017.11.025. View

15.

Sousa C, Biancur D, Wang X, Halbrook C, Sherman M, Zhang L . Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016; 536(7617):479-83. PMC: 5228623. DOI: 10.1038/nature19084. View

16.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

17.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

18.

Ananieva E . Targeting amino acid metabolism in cancer growth and anti-tumor immune response. World J Biol Chem. 2015; 6(4):281-9. PMC: 4657121. DOI: 10.4331/wjbc.v6.i4.281. View

19.

Ma E, Bantug G, Griss T, Condotta S, Johnson R, Samborska B . Serine Is an Essential Metabolite for Effector T Cell Expansion. Cell Metab. 2017; 25(2):482. DOI: 10.1016/j.cmet.2017.01.014. View

20.

Ye J, Palm W, Peng M, King B, Lindsten T, Li M . GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev. 2015; 29(22):2331-6. PMC: 4691887. DOI: 10.1101/gad.269324.115. View