Amino Acid Metabolism in Tumor Biology and Therapy

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2024 Jan 13

PMID 38218942

Authors

Jie Chen

Likun Cui

Shaoteng Lu

Sheng Xu

Affiliations

Soon will be listed here.

Abstract

Amino acid metabolism plays important roles in tumor biology and tumor therapy. Accumulating evidence has shown that amino acids contribute to tumorigenesis and tumor immunity by acting as nutrients, signaling molecules, and could also regulate gene transcription and epigenetic modification. Therefore, targeting amino acid metabolism will provide new ideas for tumor treatment and become an important therapeutic approach after surgery, radiotherapy, and chemotherapy. In this review, we systematically summarize the recent progress of amino acid metabolism in malignancy and their interaction with signal pathways as well as their effect on tumor microenvironment and epigenetic modification. Collectively, we also highlight the potential therapeutic application and future expectation.

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References

Kebede A, Schneider R, Daujat S . Novel types and sites of histone modifications emerge as players in the transcriptional regulation contest. FEBS J. 2014; 282(9):1658-74. DOI: 10.1111/febs.13047. View

Baumjohann D, Kageyama R, Clingan J, Morar M, Patel S, de Kouchkovsky D . The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression. Nat Immunol. 2013; 14(8):840-8. PMC: 3720769. DOI: 10.1038/ni.2642. 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

Karlsson E, Perez-Tenorio G, Amin R, Bostner J, Skoog L, Fornander T . The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials. Breast Cancer Res. 2013; 15(5):R96. PMC: 3978839. DOI: 10.1186/bcr3557. View

Lu J, Chen M, Tao Z, Gao S, Li Y, Cao Y . Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development and . Oncotarget. 2017; 8(44):76458-76467. PMC: 5652719. DOI: 10.18632/oncotarget.19479. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Ha H, Sirisoma N, Kuppusamy P, Zweier J, Woster P, Casero Jr R . The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci U S A. 1998; 95(19):11140-5. PMC: 21609. DOI: 10.1073/pnas.95.19.11140. 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

Mahlknecht U, Hoelzer D . Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med. 2000; 6(8):623-44. PMC: 1949974. View

10.

Geng P, Qin W, Xu G . Proline metabolism in cancer. Amino Acids. 2021; 53(12):1769-1777. DOI: 10.1007/s00726-021-03060-1. View

11.

Brito C, Naviliat M, Tiscornia A, Vuillier F, Gualco G, Dighiero G . Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol. 1999; 162(6):3356-66. View

12.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

13.

Mayers J, Wu C, Clish C, Kraft P, Torrence M, Fiske B . Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014; 20(10):1193-1198. PMC: 4191991. DOI: 10.1038/nm.3686. View

14.

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

15.

Vettore L, Westbrook R, Tennant D . New aspects of amino acid metabolism in cancer. Br J Cancer. 2019; 122(2):150-156. PMC: 7052246. DOI: 10.1038/s41416-019-0620-5. View

16.

Jia Y, Wang H, Wang Y, Wang T, Wang M, Ma M . Low expression of Bin1, along with high expression of IDO in tumor tissue and draining lymph nodes, are predictors of poor prognosis for esophageal squamous cell cancer patients. Int J Cancer. 2015; 137(5):1095-106. DOI: 10.1002/ijc.29481. View

17.

Reynolds M, Lane A, Robertson B, Kemp S, Liu Y, Hill B . Control of glutamine metabolism by the tumor suppressor Rb. Oncogene. 2013; 33(5):556-66. PMC: 3918885. DOI: 10.1038/onc.2012.635. View

18.

Zhu J, Thompson C . Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019; 20(7):436-450. PMC: 6592760. DOI: 10.1038/s41580-019-0123-5. View

19.

Willems L, Jacque N, Jacquel A, Neveux N, Trovati Maciel T, Lambert M . Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood. 2013; 122(20):3521-32. PMC: 3829119. DOI: 10.1182/blood-2013-03-493163. View

20.

Mentch S, Locasale J . One-carbon metabolism and epigenetics: understanding the specificity. Ann N Y Acad Sci. 2015; 1363:91-8. PMC: 4801744. DOI: 10.1111/nyas.12956. View