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Research paper

The amino acid transporter SLC7A11 expression in breast cancer

, , , , , , , & ORCID Icon show all
Article: 2291855 | Received 09 Jun 2023, Accepted 02 Dec 2023, Published online: 10 Dec 2023

References

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–14. doi:10.3322/caac.21660.
  • Dawson SJ, Rueda OM, Aparicio S, Caldas C. A new genome-driven integrated classification of breast cancer and its implications. EMBO J. 2013;32(5):617–628. doi:10.1038/emboj.2013.19.
  • Phan LM, Yeung SC, Lee MH. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med. 2014;11(1):1–19. doi:10.7497/j.issn.2095-3941.2014.01.001.
  • Wang Z, Liu F, Fan N, Zhou C, Li D, Macvicar T, Dong Q, Bruns CJ, Zhao Y. 2020. Targeting glutaminolysis: new perspectives to understand cancer development and novel strategies for potential target therapies. Front Oncol. 10:589508. doi:10.3389/fonc.2020.589508.
  • Matés JM, Di Paola FJ, Campos-Sandoval JA, Mazurek S, Márquez J. Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer. Semin Cell Dev Biol. 2020;98:34–43. doi:10.1016/j.semcdb.2019.05.012.
  • Choi Y-K, Park K-G. Targeting glutamine metabolism for cancer treatment. Biomol & Therapeutics. 2018;26(1):19. doi:10.4062/biomolther.2017.178.
  • Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M. The cystine/glutamate antiporter system xc− in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal. 2013;18(5):522–555. doi:10.1089/ars.2011.4391.
  • Chio IIC, Tuveson DA. Ros in cancer: the burning question. Trends Mol Med. 2017;23(5):411–429. doi:10.1016/j.molmed.2017.03.004.
  • Koppula P, Zhuang L, Gan B. Cystine transporter slc7a11/xct in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 2021;12(8):599–620. doi:10.1007/s13238-020-00789-5.
  • Zhu J, Berisa M, Schwörer S, Qin W, Cross JR, Thompson CB. Transsulfuration activity can support cell growth upon extracellular cysteine limitation. Cell Metab. 2019;30(5):865–876. e865. doi:10.1016/j.cmet.2019.09.009.
  • Wei Z, Liu X, Cheng C, Yu W, Yi P. 2021. Metabolism of amino acids in cancer. Front Cell Dev Biol. 8:603837. doi:10.3389/fcell.2020.603837.
  • Koppula P, Zhang Y, Zhuang L, Gan B. Amino acid transporter slc7a11/xct at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun. 2018;38(1):1–13. doi:10.1186/s40880-018-0288-x.
  • Lu SC. Glutathione synthesis. Biochimica et Biophysica Acta (BBA)-general subjects. Biochim et Biophys Acta (BBA) - Gen Subj. 2013;1830(5):3143–3153. doi:10.1016/j.bbagen.2012.09.008.
  • Combs JA, DeNicola GM. The non-essential amino acid cysteine becomes essential for tumor proliferation and survival. Cancers. 2019;11(5):678. doi:10.3390/cancers11050678.
  • Hu K, Li K, Lv J, Feng J, Chen J, Wu H, Cheng F, Jiang W, Wang J, Pei H. Suppression of the slc7a11/glutathione axis causes synthetic lethality in kras-mutant lung adenocarcinoma. J Clin Invest. 2020;130(4):1752–1766. doi:10.1172/JCI124049.
  • Ji X, Qian J, Rahman SJ, Siska PJ, Zou Y, Harris BK, Hoeksema MD, Trenary IA, Heidi C, Eisenberg R. Xct (slc7a11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression. Oncogene. 2018;37(36):5007–5019. doi:10.1038/s41388-018-0307-z.
  • Lin W, Wang C, Liu G, Bi C, Wang X, Zhou Q, Jin H. 2020. Slc7a11/xct in cancer: biological functions and therapeutic implications. Am J Cancer Res. 10:3106.
  • Ma Z, Zhang H, Lian M, Yue C, Dong G, Jin Y, Li R, Wan H, Wang R, Wang Y, et al. Slc7a11, a component of cysteine/glutamate transporter, is a novel biomarker for the diagnosis and prognosis in laryngeal squamous cell carcinoma. Oncol Rep. 2017;38(5):3019–3029. doi:10.3892/or.2017.5976.
  • Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, Warren PP, White DM, Reid MA, Eschbacher JM. Slc7a11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med. 2015;7(289):289ra286–289ra286. doi:10.1126/scitranslmed.aaa8103.
  • Savaskan NE, Heckel A, Hahnen E, Engelhorn T, Doerfler A, Ganslandt O, Nimsky C, Buchfelder M, Eyüpoglu IY. Small interfering rna–mediated xct silencing in gliomas inhibits neurodegeneration and alleviates brain edema. Nat Med. 2008;14(6):629–632. doi:10.1038/nm1772.
  • Sharbeen G, McCarroll JA, Akerman A, Kopecky C, Youkhana J, Kokkinos J, Holst J, Boyer C, Erkan M, Goldstein D. Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to slc7a11 inhibition. Cancer Res. 2021;81(13):3461–3479. doi:10.1158/0008-5472.CAN-20-2496.
  • Zhang L, Huang Y, Ling J, Zhuo W, Yu Z, Luo Y, Zhu Y. Overexpression of slc7a11: A novel oncogene and an indicator of unfavorable prognosis for liver carcinoma. Future Oncol. 2018;14(10):927–936. doi:10.2217/fon-2017-0540.
  • Zhu JH, De Mello RA, Yan QL, Wang JW, Chen Y, Ye QH, Wang ZJ, Tang HJ, Huang T. Mir-139-5p/slc7a11 inhibits the proliferation, invasion and metastasis of pancreatic carcinoma via pi3k/akt signaling pathway. Biochim Biophys Acta Mol Basis Dis. 2020;1866(6):165747. doi:10.1016/j.bbadis.2020.165747.
  • Lanzardo S, Conti L, Rooke R, Ruiu R, Accart N, Bolli E, Arigoni M, Macagno M, Barrera G, Pizzimenti S. Immunotargeting of antigen xct attenuates stem-like cell behavior and metastatic progression in breast cancer. Cancer Res. 2016;76(1):62–72. doi:10.1158/0008-5472.CAN-15-1208.
  • Hasegawa M, Takahashi H, Rajabi H, Alam M, Suzuki Y, Yin L, Tagde A, Maeda T, Hiraki M, Sukhatme VP. Functional interactions of the cystine/glutamate antiporter, cd44v and muc1-c oncoprotein in triple-negative breast cancer cells. Oncotarget. 2016;7(11):11756. doi:10.18632/oncotarget.7598.
  • Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, Van‘t Veer LJ. Glutamine sensitivity analysis identifies the xct antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013;24(4):450–465. doi:10.1016/j.ccr.2013.08.020.
  • Kim S, Kim DH, Jung W-H, Koo JS. Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. Endocr Relat Cancer. 2013;20(3):339–348. doi:10.1530/ERC-12-0398.
  • Kulkoyluoglu-Cotul E, Arca A, Madak-Erdogan Z. Crosstalk between estrogen signaling and breast cancer metabolism. Trends In Endocrinol Metabolism. 2019;30(1):25–38. doi:10.1016/j.tem.2018.10.006.
  • Gong Y, Ji P, Yang Y-S, Xie S, Yu T-J, Xiao Y, Jin M-L, Ma D, Guo L-W, Pei Y-C. Metabolic-pathway-based subtyping of triple-negative breast cancer reveals potential therapeutic targets. Cell Metab. 2021;33(1):51–64. e59. doi:10.1016/j.cmet.2020.10.012.
  • Verschoor ML, Singh G. Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer. Mol Cancer. 2013;12(1):138. doi:10.1186/1476-4598-12-138.
  • Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R, Gu W. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520(7545):57–62. doi:10.1038/nature14344.
  • Bhutia YD, Ganapathy V. Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta. 2016;1863(10):2531–2539. doi:10.1016/j.bbamcr.2015.12.017.
  • Nagano O, Okazaki S, Saya H. Redox regulation in stem-like cancer cells by cd44 variant isoforms. Oncogene. 2013;32(44):5191–5198. doi:10.1038/onc.2012.638.
  • Kimbung S, Johansson I, Danielsson A, Veerla S, Egyhazi Brage S, Frostvik Stolt M, Skoog L, Carlsson L, Einbeigi Z, Lidbrink E. Transcriptional profiling of breast cancer metastases identifies liver metastasis–selective genes associated with adverse outcome in luminal a primary breast cancer. Clin Cancer Res. 2016;22(1):146–157. doi:10.1158/1078-0432.CCR-15-0487.
  • Ge C, Cao B, Feng D, Zhou F, Zhang J, Yang N, Feng S, Wang G, Aa J. The down-regulation of slc7a11 enhances ros induced p-gp over-expression and drug resistance in mcf-7 breast cancer cells. Sci Rep. 2017;7(1):3791. doi:10.1038/s41598-017-03881-9.
  • Lu H, Samanta D, Xiang L, Zhang H, Hu H, Chen I, Bullen JW, Semenza GL. Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proc Natl Acad Sci U S A. 2015;112(33):E4600–4609. doi:10.1073/pnas.1513433112.
  • Polewski MD, Reveron-Thornton RF, Cherryholmes GA, Marinov GK, Cassady K, Aboody KS. Increased expression of system xc− in glioblastoma confers an altered metabolic state and temozolomide resistance. Mol Cancer Res. 2016;14(12):1229–1242. doi:10.1158/1541-7786.MCR-16-0028.
  • Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. The integrated stress response. EMBO Rep. 2016;17(10):1374–1395. doi:10.15252/embr.201642195.
  • Wolf IM, Fan Z, Rauh M, Seufert S, Hore N, Buchfelder M, Savaskan NE, Eyüpoglu IY. Histone deacetylases inhibition by saha/vorinostat normalizes the glioma microenvironment via xct equilibration. Sci Rep. 2014;4(1):6226. doi:10.1038/srep06226.
  • Ye P, Mimura J, Okada T, Sato H, Liu T, Maruyama A, Ohyama C, Itoh K. Nrf2- and atf4-dependent upregulation of xct modulates the sensitivity of t24 bladder carcinoma cells to proteasome inhibition. Mol Cell Biol. 2014;34(18):3421–3434. doi:10.1128/mcb.00221-14.
  • Chen D, Fan Z, Rauh M, Buchfelder M, Eyupoglu IY, Savaskan N. Atf4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xct-dependent manner. Oncogene. 2017;36(40):5593–5608. doi:10.1038/onc.2017.146.
  • Chen D, Rauh M, Buchfelder M, Eyupoglu IY, Savaskan N. The oxido-metabolic driver atf4 enhances temozolamide chemo-resistance in human gliomas. Oncotarget. 2017;8(31):51164–51176. doi:10.18632/oncotarget.17737.
  • Liu T, Jiang L, Tavana O, Gu W. The deubiquitylase otub1 mediates ferroptosis via stabilization of slc7a11. Cancer Res. 2019;79(8):1913–1924. doi:10.1158/0008-5472.can-18-3037.
  • Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H. Cd44 variant regulates redox status in cancer cells by stabilizing the xct subunit of system xc− and thereby promotes tumor growth. Cancer Cell. 2011;19(3):387–400. doi:10.1016/j.ccr.2011.01.038.
  • Wada F, Koga H, Akiba J, Niizeki T, Iwamoto H, Ikezono Y, Nakamura T, Abe M, Masuda A, Sakaue T. High expression of cd 44v9 and xct in chemoresistant hepatocellular carcinoma: potential targets by sulfasalazine. Cancer Sci. 2018;109(9):2801–2810. doi:10.1111/cas.13728.
  • Ju H-Q, Lu Y-X, Chen D-L, Tian T, Mo H-Y, Wei X-L, Liao J-W, Wang F, Zeng Z-L, Pelicano H. Redox regulation of stem-like cells though the cd44v-xct axis in colorectal cancer: mechanisms and therapeutic implications. Theranostics. 2016;6(8):1160. doi:10.7150/thno.14848.
  • Fairweather SJ, Shah N, Brӧer S.Heteromeric solute carriers: function, structure, pathology and pharmacology.Protein Reviews. 21. 2021:13–127. doi:10.1007/5584_2020_584.
  • Fotiadis D, Kanai Y, Palacín M. The slc3 and slc7 families of amino acid transporters. Mol Aspects Med. 2013;34(2–3):139–158. doi:10.1016/j.mam.2012.10.007.
  • Kandasamy P, Gyimesi G, Kanai Y, Hediger MA. Amino acid transporters revisited: new views in health and disease. Trends Biochem Sci. 2018;43(10):752–789. doi:10.1016/j.tibs.2018.05.003.
  • Shin C-S, Mishra P, Watrous JD, Carelli V, D’Aurelio M, Jain M, Chan DC. The glutamate/cystine xct antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun. 2017;8(1):1–11. doi:10.1038/ncomms15074.
  • Liu DS, Duong CP, Haupt S, Montgomery KG, House CM, Azar WJ, Pearson HB, Fisher OM, Read M, Guerra GR, et al. Inhibiting the system xC−/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun. 2017;8(1):14844. doi:10.1038/ncomms14844.
  • Muir A, Danai LV, Gui DY, Waingarten CY, Lewis CA, Vander Heiden MG. 2017. Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. eLife. 6. doi:10.7554/eLife.27713
  • Lampa M, Arlt H, He T, Ospina B, Reeves J, Zhang B, Murtie J, Deng G, Barberis C, Hoffmann D, et al. Glutaminase is essential for the growth of triple-negative breast cancer cells with a deregulated glutamine metabolism pathway and its suppression synergizes with mtor inhibition. PLoS ONE. 2017;12(9):e0185092. doi:10.1371/journal.pone.0185092.
  • Fumagalli C, Ranghiero A, Gandini S, Corso F, Taormina S, De Camilli E, Rappa A, Vacirca D, Viale G, Guerini-Rocco E. Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses. Breast Cancer Res. 2020;22(1):1–11. doi:10.1186/s13058-020-01345-z.
  • Shroff EH, Eberlin LS, Dang VM, Gouw AM, Gabay M, Adam SJ, Bellovin DI, Tran PT, Philbrick WM, Garcia-Ocana A, et al. Myc oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci USA. 2015;112(21):6539–6544. doi:10.1073/pnas.1507228112.
  • Li Y, Li N, Shi J, Ahmed T, Liu H, Guo J, Tang W, Guo Y, Zhang Q. 2019. Involvement of glutathione depletion in selective cytotoxicity of oridonin to p53-mutant esophageal squamous carcinoma cells. Front Oncol. 9:1525. doi:10.3389/fonc.2019.01525.
  • Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013;493(7433):542–546. doi:10.1038/nature11743.
  • Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, et al. Prognostic significance of amino-acid transporter expression (lat1, asct2, and xct) in surgically resected tongue cancer. Br J Cancer. 2014;110(10):2506–2513. doi:10.1038/bjc.2014.178.
  • Davey MG, Hynes SO, Kerin MJ, Miller N, Lowery AJ. Ki-67 as a prognostic biomarker in invasive breast cancer. Cancers Basel. 2021;13(17):4455. doi:10.3390/cancers13174455.
  • Uribe-Querol E, Rosales C Neutrophils in cancer: two sides of the same coin. J Immunol res. 2015.
  • Nagasaki T, Schuyler AJ, Zhao J, Samovich SN, Yamada K, Deng Y, Ginebaugh SP, Christenson SA, Woodruff PG, Fahy JV. 15lo1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation. J Clin Invest. 2022;132(1):132. doi:10.1172/JCI151685.
  • Yang Y, Wang Y, Guo L, Gao W, Tang T-L, Yan M. Interaction between macrophages and ferroptosis. Cell Death Disease. 2022;13(4):355. doi:10.1038/s41419-022-04775-z.
  • Goodall GJ, Wickramasinghe VO. Rna in cancer. Nat Rev Cancer. 2021;21(1):22–36. doi:10.1038/s41568-020-00306-0.
  • Itai Y, Rappoport N, Shamir R. Integration of gene expression and DNA methylation data across different experiments. Nucleic Acids Res. 2023;51(15):7762–7776. doi:10.1093/nar/gkad566.
  • Lu H, Zhou Q, He J, Jiang Z, Peng C, Tong R, Shi J. Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials. Signal Transduct Target Ther. 2020;5(1):213. doi:10.1038/s41392-020-00315-3.
  • Statello L, Guo C-J, Chen L-L, Huarte M. Gene regulation by long non-coding rnas and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118. doi:10.1038/s41580-020-00315-9.
  • Alla AS. Transcription factor trapping by RNA in gene regulatory elements. Science. 2015;350:978–981. doi:10.1126/science.aad3346.
  • Curtis C, Shah SP, Chin S-F, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486(7403):346. doi:10.1038/nature10983.
  • Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, XS L. Timer: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77(21):e108–e110. doi:10.1158/0008-5472.CAN-17-0307.
  • Modhukur V, Iljasenko T, Metsalu T, Lokk K, Laisk-Podar T, Vilo J. 2018. Methsurv: a web tool to perform multivariable survival analysis using DNA methylation data. Epigenomics. 10:277–288. doi:10.2217/epi-2017-0118.
  • Green A, Powe D, Rakha E, Soria D, Lemetre C, Nolan C, Barros F, Macmillan R, Garibaldi J, Ball G. Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers. Br J Cancer. 2013;109(7):1886–1894. doi:10.1038/bjc.2013.528.
  • Meyerholz DK, Beck AP. Principles and approaches for reproducible scoring of tissue stains in research. Lab Invest. 2018;98(7):844–855. doi:10.1038/s41374-018-0057-0.
  • Green AR, Aleskandarany MA, Agarwal D, Elsheikh S, Nolan CC, Diez-Rodriguez M, Macmillan RD, Ball GR, Caldas C, Madhusudan S, et al. Myc functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. Br J Cancer. 2016;114(8):917–928. doi:10.1038/bjc.2016.46.
  • Craze ML, El-Ansari R, Aleskandarany MA, Cheng KW, Alfarsi L, Masisi B, Diez-Rodriguez M, Nolan CC, Ellis IO, Rakha EA, et al. Glutamate dehydrogenase (glud1) expression in breast cancer. Breast Cancer Res Treat. 2019;174(1):79–91. doi:10.1007/s10549-018-5060-z.
  • El Ansari R, Alfarsi L, Craze ML, Masisi BK, Ellis IO, Rakha EA, Green AR. The solute carrier slc7a8 is a marker of favourable prognosis in er-positive low proliferative invasive breast cancer. Breast Cancer Res Treat. 2020;181(1):1–12. doi:10.1007/s10549-020-05586-6.
  • El Ansari R, Craze ML, Miligy I, Diez-Rodriguez M, Nolan CC, Ellis IO, Rakha EA, Green AR. The amino acid transporter slc7a5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal b tumours. Breast Cancer Res. 2018;20(1):21. doi:10.1186/s13058-018-0946-6.
  • Morotti M, Zois CE, El-Ansari R, Craze ML, Rakha EA, Fan SJ, Valli A, Haider S, Goberdhan DCI, Green AR, et al. Increased expression of glutamine transporter snat2/slc38a2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer. Br J Cancer. 2020;124(2):10.1038/s41416-020-01113–y. doi:10.1038/s41416-020-01113-y.
  • Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–410. 2002;41: 151-152, discussion 152-153. doi:10.1111/j.1365-2559.1991.tb00229.x.
  • Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S, Cardoso F. Primary breast cancer: Esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(5):v8–30. doi:10.1093/annonc/mdv298.