Apoptotic caspases inhibit abscopal responses to radiation and identify a new prognostic biomarker for breast cancer patients

References

• Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ. 2018;25:486–541. doi:10.1038/s41418-017-0012-4.
   PubMed Web of Science ®Google Scholar
• Fuchs Y, Steller H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol. 2015;16:329–344. doi:10.1038/nrm3999.
   PubMed Web of Science ®Google Scholar
• Green DR, Galluzzi L, Kroemer G. Cell biology. Metabolic control of cell death. Science. 2014;345:1250256.
   PubMed Web of Science ®Google Scholar
• Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11:621–632. doi:10.1038/nrm2952.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70. doi:10.1016/s0092-8674(00)81683-9.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674. doi:10.1016/j.cell.2011.02.013.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Chan TA, Kroemer G, Wolchok JD, Lopez-Soto A. The hallmarks of successful anticancer immunotherapy. Sci Transl Med. 2018;10. doi:10.1126/scitranslmed.aao4496.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell. 2015;28:690–714. doi:10.1016/j.ccell.2015.10.012.
   PubMed Web of Science ®Google Scholar
• Ichim G, Tait SW. A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer. 2016;16:539–548. doi:10.1038/nrc.2016.58.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Yamazaki T, Kroemer G. Linking cellular stress responses to systemic homeostasis. Nat Rev Mol Cell Biol. 2018;19:731–745. doi:10.1038/s41580-018-0068-0.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Lopez-Soto A, Kumar S, Kroemer G. Caspases connect cell-death signaling to organismal homeostasis. Immunity. 2016;44:221–231. doi:10.1016/j.immuni.2016.01.020.
   PubMed Web of Science ®Google Scholar
• Yatim N, Cullen S, Albert ML. Dying cells actively regulate adaptive immune responses. Nat Rev Immunol. 2017;17:262–275. doi:10.1038/nri.2017.9.
   PubMed Web of Science ®Google Scholar
• Kiss RS, Elliott MR, Ma Z, Marcel YL, Ravichandran KS. Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes. Curr Biol. 2006;16:2252–2258. doi:10.1016/j.cub.2006.09.043.
   PubMed Web of Science ®Google Scholar
• Li MO, Sarkisian MR, Mehal WZ, Rakic P, Flavell RA. Phosphatidylserine receptor is required for clearance of apoptotic cells. Science. 2003;302:1560–1563. doi:10.1126/science.1087621.
   PubMed Web of Science ®Google Scholar
• Segawa K, Kurata S, Yanagihashi Y, Brummelkamp TR, Matsuda F, Nagata S. Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. Science. 2014;344:1164–1168. doi:10.1126/science.1252809.
   PubMed Web of Science ®Google Scholar
• Suzuki J, Denning DP, Imanishi E, Horvitz HR, Nagata S. Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science. 2013;341:403–406. doi:10.1126/science.1236758.
   PubMed Web of Science ®Google Scholar
• Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O'Sullivan B, He Z, Peng Y, Tan AC, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011;17:860–866. doi:10.1038/nm.2385.
   PubMed Web of Science ®Google Scholar
• Zelenay S, van der Veen AG, Bottcher JP, Snelgrove KJ, Rogers N, Acton SE, Chakravarty P, Girotti MR, Marais R, Quezada SA, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell. 2015;162:1257–1270. doi:10.1016/j.cell.2015.08.015.
   PubMed Web of Science ®Google Scholar
• Lauber K, Bohn E, Krober SM, Xiao YJ, Blumenthal SG, Lindemann RK, Marini P, Wiedig C, Zobywalski A, Baksh S, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 2003;113:717–730. doi:10.1016/s0092-8674(03)00422-7.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Vanpouille-Box C, Bakhoum SF, Demaria S. SnapShot: CGAS-STING signaling. Cell. 2018;173:276–276 e271. doi:10.1016/j.cell.2018.03.015.
   PubMed Web of Science ®Google Scholar
• Rongvaux A, Jackson R, Harman CC, Li T, West AP, de Zoete MR, Wu Y, Yordy B, Lakhani SA, Kuan CY, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563–1577. doi:10.1016/j.cell.2014.11.037.
   PubMed Web of Science ®Google Scholar
• White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC, Herold MJ, van Delft MF, Bedoui S, Lessene G, Ritchie ME, et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell. 2014;159:1549–1562. doi:10.1016/j.cell.2014.11.036.
   PubMed Web of Science ®Google Scholar
• McArthur K, Whitehead LW, Heddleston JM, Li L, Padman BS, Oorschot V, Geoghegan ND, Chappaz S, Davidson S, San Chin H, et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science. 2018;359. doi:10.1126/science.aao6047.
   PubMed Web of Science ®Google Scholar
• Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017;8:15618. doi:10.1038/ncomms15618.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, et al. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ. 2009;16:1093–1107. doi:10.1038/cdd.2009.44.
   PubMed Web of Science ®Google Scholar
• Morselli E, Shen S, Ruckenstuhl C, Bauer MA, Marino G, Galluzzi L, Criollo A, Michaud M, Maiuri MC, Chano T, et al. p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200. Cell Cycle. 2011;10:2763–2769. doi:10.4161/cc.10.16.16868.
   PubMed Web of Science ®Google Scholar
• Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O, Senovilla L, Talhaoui I, Guegan J, Enot DP, et al. Cisplatin resistance associated with PARP hyperactivation. Cancer Res. 2013;73:2271–2280. doi:10.1158/0008-5472.CAN-12-3000.
   PubMed Web of Science ®Google Scholar
• Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47. doi:10.1093/nar/gkv007.
   PubMed Web of Science ®Google Scholar
• Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32:2847–2849. doi:10.1093/bioinformatics/btw313.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Baehrecke H, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, et al. Molecular definitions of autophagy and related processes. Embo J. 2017;36:1811–1836. doi:10.15252/embj.201796697.
   PubMed Web of Science ®Google Scholar
• Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486:346–352. doi:10.1038/nature10983.
   PubMed Web of Science ®Google Scholar
• Weichselbaum RR, Ishwaran H, Yoon T, Nuyten DS, Baker SW, Khodarev N, Su AW, Shaikh AY, Roach P, Kreike B, et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc Natl Acad Sci U S A. 2008;105:18490–18495. doi:10.1073/pnas.0809242105.
   PubMed Web of Science ®Google Scholar
• Erdal E, Haider S, Rehwinkel J, Harris AL, McHugh PJ. A prosurvival DNA damage-induced cytoplasmic interferon response is mediated by end resection factors and is limited by Trex1. Genes Dev. 2017;31:353–369. doi:10.1101/gad.289769.116.
   PubMed Web of Science ®Google Scholar
• Obacz J, Brychtova V, Podhorec J, Fabian P, Dobes P, Vojtesek B, Hrstka R. Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients. Onco Targets Ther. 2015;8:1523–1532. doi:10.2147/OTT.S82235.
   PubMedGoogle Scholar
• Chen C, Qin F, Zhang H, Liu X, Guo C, Zhang M, Gu F, Fu L, Ma Y. Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer. Cancer Biol Ther. 2015;16:856–865. doi:10.1080/15384047.2015.1040957.
   PubMed Web of Science ®Google Scholar
• Bokobza SM, Ye L, Kynaston HE, Mansel RE, Jiang WG. Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells. Cancer Genomics Proteomics. 2009;6:101–108.
   PubMedGoogle Scholar
• Dai K, Qin F, Zhang H, Liu X, Guo C, Zhang M, Gu F, Fu L, Ma Y. Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy. Oncotarget. 2016;7:4770–4784. doi:10.18632/oncotarget.6613.
   PubMedGoogle Scholar
• Esseghir S, Kennedy A, Seedhar P, Nerurkar A, Poulsom R, Reis-Filho JS, Isacke CM. Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in a screen for signal sequence encoding proteins. Clin Cancer Res. 2007;13:3164–3173. doi:10.1158/1078-0432.CCR-07-0224.
   PubMed Web of Science ®Google Scholar
• Coulson-Gilmer C, Humphries MP, Sundara Rajan S, Droop A, Jackson S, Condon A, Cserni G, Jordan LB, Jones LJ, Kanthan R, et al. Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer. J Pathol Clin Res. 2018;4:241–249. doi:10.1002/cjp2.106.
   PubMedGoogle Scholar
• Aushev VN, Lee E, Zhu J, Gopalakrishnan K, Li Q, Teitelbaum SL, Wetmur J, Degli Esposti D, Hernandez-Vargas H, Herceg Z, et al. Novel predictors of breast cancer survival derived from miRNA activity analysis. Clin Cancer Res. 2018;24:581–591. doi:10.1158/1078-0432.CCR-17-0996.
   PubMed Web of Science ®Google Scholar
• Franzen B, Alexeyenko A, Kamali-Moghaddam M, Hatschek T, Kanter L, Ramqvist T, Kierkegaard J, Masucci G, Auer G, Landegren U, et al. Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer. Mol Oncol. 2019;13:376–391. doi:10.1002/1878-0261.12410.
   PubMed Web of Science ®Google Scholar
• Ma X, Norsworthy K, Kundu N, Rodgers WH, Gimotty PA, Goloubeva O, Lipsky M, Li Y, Holt D, Fulton A. CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model. Mol Cancer Ther. 2009;8:490–498. doi:10.1158/1535-7163.MCT-08-0485.
   PubMed Web of Science ®Google Scholar
• Debald M, Schildberg FA, Linke A, Walgenbach K, Kuhn W, Hartmann G, Walgenbach-Brunagel G. Specific expression of k63-linked ubiquitination of calmodulin-like protein 5 in breast cancer of premenopausal patients. J Cancer Res Clin Oncol. 2013;139:2125–2132. doi:10.1007/s00432-013-1541-y.
   PubMed Web of Science ®Google Scholar
• Murray GI, Patimalla S, Stewart KN, Miller ID, Heys SD. Profiling the expression of cytochrome P450 in breast cancer. Histopathology. 2010;57:202–211. doi:10.1111/j.1365-2559.2010.03606.x.
   PubMed Web of Science ®Google Scholar
• Hyman BT, Yuan J. Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci. 2012;13:395–406. doi:10.1038/nrn3228.
   PubMed Web of Science ®Google Scholar
• Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat Rev Cardiol. 2019;16:33–55. doi:10.1038/s41569-018-0074-0.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M, et al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2015;22:58–73. doi:10.1038/cdd.2014.137.
   PubMed Web of Science ®Google Scholar
• Ning X, Wang Y, Jing M, Sha M, Lv M, Gao P, Zhang R, Huang X, Feng JM, Jiang Z. Apoptotic Caspases suppress Type I interferon production via the cleavage of cGAS, MAVS, and IRF3. Mol Cell. 2019;74:19–31 e17. doi:10.1016/j.molcel.2019.02.013.
   PubMed Web of Science ®Google Scholar
• Vanpouille-Box C, Demaria S, Formenti SC, Galluzzi L. Cytosolic DNA sensing in organismal tumor control. Cancer Cell. 2018;34:361–378. doi:10.1016/j.ccell.2018.05.013.
   PubMed Web of Science ®Google Scholar
• Coburn LA, Singh K, Asim M, Barry DP, Allaman MM, Al-Greene NT, Hardbower DM, Polosukhina D, Williams CS, Delgado AG, et al. Loss of solute carrier family 7 member 2 exacerbates inflammation-associated colon tumorigenesis. Oncogene. 2019;38:1067–1079.
   PubMed Web of Science ®Google Scholar
• Cimen Bozkus C, Elzey BD, Crist SA, Ellies LG, Ratliff TL. Expression of cationic amino acid transporter 2 is required for myeloid-derived suppressor cell-mediated control of T cell immunity. J Immunol. 2015;195:5237–5250. doi:10.4049/jimmunol.1500959.
   PubMed Web of Science ®Google Scholar
• Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2017;66:180–190. doi:10.1136/gutjnl-2016-312431.
   PubMed Web of Science ®Google Scholar
• Shiffman M, Freilich B, Vuppalanchi R, Watt K, Chan JL, Spada A, Hagerty DT, Schiff E. Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2019;49:64–73. doi:10.1111/apt.15030.
   PubMed Web of Science ®Google Scholar
• Mehta G, Rousell S, Burgess G, Morris M, Wright G, McPherson S, Frenette C, Cave M, Hagerty DT, Spada A, et al. A placebo-controlled, multicenter, double-blind, phase 2 randomized trial of the pan-caspase inhibitor emricasan in patients with acutely decompensated cirrhosis. J Clin Exp Hepatol. 2018;8:224–234. doi:10.1016/j.jceh.2017.11.006.
   PubMed Web of Science ®Google Scholar