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أعرض في EDS

Asparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP-ALL cell survival and a potential therapeutic target.

التفاصيل البيبلوغرافية
العنوان: Asparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP-ALL cell survival and a potential therapeutic target.
المؤلفون: Taurino G; Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy., Dander E; Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy., Chiu M; Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy., Pozzi G; Laboratory of Human Anatomy, Department of Medicine and Surgery, University of Parma, Parma, Italy., Maccari C; Laboratory of Industrial Toxicology, Department of Medicine and Surgery, University of Parma, Parma, Italy., Starace R; Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy., Silvestri D; Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy., Griffini E; Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy., Bianchi MG; Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy.; MRH-Microbiome Research Hub, Parco Area Delle Scienze 11/A, University of Parma, Parma, Italy., Carubbi C; Laboratory of Human Anatomy, Department of Medicine and Surgery, University of Parma, Parma, Italy., Andreoli R; Laboratory of Industrial Toxicology, Department of Medicine and Surgery, University of Parma, Parma, Italy.; CERT-Center of Excellence for Toxicological Research, University of Parma, Parma, Italy., Mirandola P; Laboratory of Human Anatomy, Department of Medicine and Surgery, University of Parma, Parma, Italy., Valsecchi MG; Biostatistics and Clinical Epidemiology, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.; School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy., Rizzari C; Department of Pediatrics, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy., D'Amico G; Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy., Bussolati O; Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy.; MRH-Microbiome Research Hub, Parco Area Delle Scienze 11/A, University of Parma, Parma, Italy.
المصدر: British journal of haematology [Br J Haematol] 2024 Jul; Vol. 205 (1), pp. 175-188. Date of Electronic Publication: 2024 May 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications
مواضيع طبية MeSH: Amino Acid Transport System ASC*/metabolism , Amino Acid Transport System ASC*/genetics , Asparagine*/metabolism , Minor Histocompatibility Antigens*/metabolism , Minor Histocompatibility Antigens*/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/genetics , Cell Survival*/drug effects, Humans ; Amino Acid Transport System A/metabolism ; Amino Acid Transport System A/genetics ; Cell Line, Tumor ; Asparaginase/pharmacology ; Asparaginase/therapeutic use ; Cell Proliferation/drug effects ; Child
مستخلص: B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) blasts strictly depend on the transport of extra-cellular asparagine (Asn), yielding a rationale for L-asparaginase (ASNase) therapy. However, the carriers used by ALL blasts for Asn transport have not been identified yet. Exploiting RS4;11 cells as BCP-ALL model, we have found that cell Asn is lowered by either silencing or inhibition of the transporters ASCT2 or SNAT5. The inhibitors V-9302 (for ASCT2) and GluγHA (for SNAT5) markedly lower cell proliferation and, when used together, suppress mTOR activity, induce autophagy and cause a severe nutritional stress, leading to a proliferative arrest and a massive cell death in both the ASNase-sensitive RS4;11 cells and the relatively ASNase-insensitive NALM-6 cells. The cytotoxic effect is not prevented by coculturing leukaemic cells with primary mesenchymal stromal cells. Leukaemic blasts of paediatric ALL patients express ASCT2 and SNAT5 at diagnosis and undergo marked cytotoxicity when exposed to the inhibitors. ASCT2 expression is positively correlated with the minimal residual disease at the end of the induction therapy. In conclusion, ASCT2 and SNAT5 are the carriers exploited by ALL cells to transport Asn, and ASCT2 expression is associated with a lower therapeutic response. ASCT2 may thus represent a novel therapeutic target in BCP-ALL.
(© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
References: Darvishi F, Jahanafrooz Z, Mokhtarzadeh A. Microbial L‐asparaginase as a promising enzyme for treatment of various cancers. Appl Microbiol Biotechnol. 2022;106(17):5335–5347.
Maese L, Rau RE. Current use of Asparaginase in acute lymphoblastic leukemia/lymphoblastic lymphoma. Front Pediatr. 2022;10:902117.
Chiu M, Taurino G, Bianchi MG, Kilberg MS, Bussolati O. Asparagine Synthetase in cancer: beyond acute lymphoblastic leukemia. Front Oncol. 2020;9:1480.
Chen SH. Asparaginase therapy in pediatric acute lymphoblastic leukemia: a focus on the mode of drug resistance. Pediatr Neonatol. 2015;56(5):287–293.
Appel IM, den Boer ML, Meijerink JPP, Veerman AJP, Reniers NCM, Pieters R. Up‐regulation of asparagine synthetase expression is not linked to the clinical response to L‐asparaginase in pediatric acute lymphoblastic leukemia. Blood. 2006;107(11):4244–4249.
Watanabe A, Miyake K, Nordlund J, Syvanen AC, van der Weyden L, Honda H, et al. Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP‐ALL. Blood. 2020;136(20):2319–2333.
Hlozkova K, Pecinova A, Alquezar‐Artieda N, Pajuelo‐Reguera D, Simcikova M, Hovorkova L, et al. Metabolic profile of leukemia cells influences treatment efficacy of L‐asparaginase. BMC Cancer. 2020;20(1):526.
Hinze L, Pfirrmann M, Karim S, Degar J, McGuckin C, Vinjamur D, et al. Synthetic lethality of Wnt pathway activation and Asparaginase in drug‐resistant acute Leukemias. Cancer Cell. 2019;35(4):664–676.
Jiang J, Srivastava S, Seim G, Pavlova NN, King B, Zou LH, et al. Promoter demethylation of the asparagine synthetase gene is required for ATF4‐dependent adaptation to asparagine depletion. J Biol Chem. 2019;294(49):18674–18684.
Touzart A, Lengline E, Latiri M, Belhocine M, Smith C, Thomas X, et al. Epigenetic silencing affects L‐Asparaginase sensitivity and predicts outcome in T‐ALL. Clin Cancer Res. 2019;25(8):2483–2493.
Ferguson DC, McCorkle JR, Barnett KR, Bonten EJ, Bergeron BP, Bhattarai KR, et al. Amino acid stress response genes promote L‐asparaginase resistance in pediatric acute lymphoblastic leukemia. Blood Adv. 2022;6(11):3386–3397.
Fallati A, Di Marzo N, D'Amico G, Dander E. Mesenchymal stromal cells (MSCs): an ally of B‐cell acute lymphoblastic leukemia (B‐ALL) cells in disease maintenance and progression within the bone marrow hematopoietic niche. Cancer. 2022;14(14):3303.
Chiu M, Taurino G, Dander E, Bardelli D, Fallati A, Andreoli R, et al. ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment. Blood Adv. 2021;5(23):5164–5178.
Pochini L, Scalise M, Galluccio M, Indiveri C. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front Chem. 2014;2:61.
Bussolati O, Laris PC, Rotoli BM, Dallasta V, Gazzola GC. Transport‐system Asc for neutral amino‐acids—an electroneutral sodium amino‐acid cotransport sensitive to the membrane‐potential. J Biol Chem. 1992;267(12):8330–8335.
Scalise M, Pochini L, Panni S, Pingitore P, Hedfalk K, Indiveri C. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5). Amino Acids. 2014;46(11):2463–2475.
Broer S. The SLC38 family of sodium‐amino acid co‐transporters. Pflug Arch Eur J Phy. 2014;466(1):155–172.
Ratei R, Basso G, Dworzak M, Gaipa G, Veltroni M, Rhein P, et al. Monitoring treatment response of childhood precursor B‐cell acute lymphoblastic leukemia in the AIEOP‐BFM‐ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. Leukemia. 2009;23(3):528–534.
Schumich A, Maurer‐Granofszky M, Attarbaschi A, Potschger U, Buldini B, Gaipa G, et al. Flow‐cytometric minimal residual disease monitoring in blood predicts relapse risk in pediatric B‐cell precursor acute lymphoblastic leukemia in trial AIEOP‐BFM‐ALL 2000. Pediatr Blood Cancer. 2019;66(5):e27590.
Basso G, Veltroni M, Valsecchi MG, Dworzak MN, Ratei R, Silvestri D, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow Cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol. 2009;27(31):5168–5174.
Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer‐Grumayer R, Moricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B‐cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP‐BFM ALL 2000 study. Blood. 2010;115(16):3206–3214.
Andre V, Longoni D, Bresolin S, Cappuzzello C, Dander E, Galbiati M, et al. Mesenchymal stem cells from Shwachman‐diamond syndrome patients display normal functions and do not contribute to hematological defects. Blood Cancer J. 2012;2(10):e94.
Low SY, Taylor PM, Ahmed A, Pogson CI, Rennie MJ. Substrate‐specificity of glutamine transporters in membrane‐vesicles from rat‐liver and skeletal‐muscle investigated using amino‐acid‐analogs. Biochem J. 1991;278:105–111.
Baird FE, Beattie KJ, Hyde AR, Ganapathy V, Rennie MJ, Taylor PM. Bidirectional substrate fluxes through the system N (SNAT5) glutamine transporter may determine net glutamine flux in rat liver. J Physiol‐London. 2004;559(2):367–381.
Schulte ML, Fu A, Zhao P, Li J, Geng L, Smith ST, et al. Pharmacological blockade of ASCT2‐dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat Med. 2018;24(2):194–202.
Hope HC, Brownlie RJ, Fife CM, Steele L, Lorger M, Salmond RJ. Coordination of asparagine uptake and asparagine synthetase expression modulates CD8(+) T cell activation. Jci Insight. 2021;6(9):e137761.
Huang H, Vandekeere S, Kalucka J, Bierhansl L, Zecchin A, Bruning U, et al. Role of glutamine and interlinked asparagine metabolism in vessel formation. EMBO J. 2017;36(16):2334–2352.
Chiu M, Toscani D, Marchica V, Taurino G, Costa F, Bianchi MG, et al. Myeloma cells deplete bone marrow glutamine and inhibit osteoblast differentiation limiting asparagine availability. Cancer. 2020;12(11):3267.
Wu J, Li G, Li L, Li D, Dong ZJ, Jiang P. Asparagine enhances LCK signalling to potentiate CD8(+) T‐cell activation and anti‐tumour responses. Nat Cell Biol. 2021;23(1):75–86.
Sharma D, Yu YL, Shen LY, Zhang GF, Karner CM. SLC1A5 provides glutamine and asparagine necessary for bone development in mice. Elife. 2021;10:e71595.
Kilberg MS, Handlogten ME, Christensen HN. Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs. J Biol Chem. 1980;255(9):4011–4019.
Hundal HS, Rennie MJ, Watt PW. Characteristics of L‐glutamine transport in perfused rat skeletal‐muscle. J Physiol‐London. 1987;393:283–305.
Fairweather SJ, Okada S, Gauthier‐Coles G, Javed K, Broer A, Broer S. A GC‐MS/single‐cell method to evaluate membrane transporter substrate specificity and signaling. Front Mol Biosci. 2021;8:646574.
Hashim M, Yokoi N, Takahashi H, Gheni G, Okechi OS, Hayami T, et al. Inhibition of SNAT5 induces incretin‐responsive state from incretin‐unresponsive state in pancreatic beta‐cells: study of ‐cell spheroid clusters as a model. Diabetes. 2018;67(9):1795–1806.
Prelowska MK, Mehlich D, Ugurlu MT, Kedzierska H, Cwiek A, Kosnik A, et al. Inhibition of the L‐glutamine transporter ASCT2 sensitizes plasma cell myeloma cells to proteasome inhibitors. Cancer Lett. 2021;507:13–25.
Ni F, Yu WM, Li Z, Graham DK, Jin L, Kang S, et al. Critical role of ASCT2‐mediated amino acid metabolism in promoting leukaemia development and progression. Nat Metab. 2019;1(3):390–403.
Meng D, Yang Q, Wang H, Melick CH, Navlani R, Frank AR, et al. Glutamine and asparagine activate mTORC1 independently of rag GTPases. J Biol Chem. 2020;295(10):2890–2899.
Buono R, Alhaddad M, Fruman DA. Novel pharmacological and dietary approaches to target mTOR in B‐cell acute lymphoblastic leukemia. Front Oncol. 2023;13:1162694.
Chiu M, Taurino G, Bianchi MG, Dander E, Fallati A, Giuliani N, et al. Functional consequences of Low activity of transport system a for neutral amino acids in human bone marrow mesenchymal stem cells. Int J Mol Sci. 2020;21(5):1899.
Taurino G, Deshmukh R, Villar VH, Chiu M, Shaw R, Hedley A, et al. Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis. Mol Metab. 2022;63:101532.
Grima‐Reyes M, Vandenberghe A, Nemazanyy I, Meola P, Paul R, Reverso‐Meinietti J, et al. Tumoral microenvironment prevents de novo asparagine biosynthesis in B cell lymphoma, regardless of ASNS expression. Sci Adv. 2022;8(27):eabn6491.
Chan WK, Lorenzi PL, Anishkin A, Purwaha P, Rogers DM, Sukharev S, et al. The glutaminase activity of L‐asparaginase is not required for anticancer activity against ASNS‐negative cells. Blood. 2014;123(23):3596–3606.
Liu Y, Zhao TL, Li ZZ, Wang L, Yuan ST, Sun L. The role of ASCT2 in cancer: a review. Eur J Pharmacol. 2018;837:81–87.
Bolzoni M, Chiu M, Accardi F, Vescovini R, Airoldi I, Storti P, et al. Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target. Blood. 2016;128(5):667–679.
Butler M, Schenau DSV, Yu JY, Jenni S, Dobay MP, Hagelaar R, et al. BTK inhibition sensitizes acute lymphoblastic leukemia to asparaginase by suppressing the amino acid response pathway. Blood. 2021;138(23):2383–2395.
Jiang J, Batra S, Zhang J. Asparagine: a metabolite to Be targeted in cancers. Metabolites. 2021;11(6):402.
Dufour E, Gay F, Aguera K, Scoazec JY, Horand F, Lorenzi PL, et al. Pancreatic tumor sensitivity to plasma L‐asparagine starvation. Pancreas. 2012;41(6):940–948.
Knott SRV, Wagenblast E, Khan S, Kim SY, Soto M, Wagner M, et al. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature. 2018;556(7699):135.
Taurino G, Chiu M, Bianchi MG, Griffini E, Bussolati O. The SLC38A5/SNAT5 amino acid transporter: from pathophysiology to pro‐cancer roles in the tumor microenvironment. Am J Physiol Cell Physiol. 2023;325(2):C550–C562.
Sniegowski T, Rajasekaran D, Sennoune SR, Sunitha S, Chen F, Fokar M, et al. Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer. Sci Rep. 2023;13(1):16863.
Chen H, Yang W, Ma L, Li Y, Ji Z. Machine‐learning based integrating bulk and single‐cell RNA sequencing reveals the SLC38A5‐CCL5 signaling as a promising target for clear cell renal cell carcinoma treatment. Transl Oncol. 2023;38:101790.
معلومات مُعتمدة: International Myeloma Foundation; IG 2019 Id.23354 Associazione Italiana per la Ricerca sul Cancro; 2022C5RHRT MUR-Italian Ministry of University and Research
فهرسة مساهمة: Keywords: L‐asparaginase; acute lymphoblastic leukaemia; asparagine; bone marrow niche; glutamine; tumour microenvironment
المشرفين على المادة: 0 (Amino Acid Transport System ASC)
0 (SLC1A5 protein, human)
7006-34-0 (Asparagine)
0 (Minor Histocompatibility Antigens)
0 (Amino Acid Transport System A)
EC 3.5.1.1 (Asparaginase)
تواريخ الأحداث: Date Created: 20240513 Date Completed: 20240712 Latest Revision: 20240712
رمز التحديث: 20240712
DOI: 10.1111/bjh.19516
PMID: 38736325
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2141
DOI:10.1111/bjh.19516