2,007
Views
0
CrossRef citations to date
0
Altmetric
Research Paper

AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer

ORCID Icon, , , , , & show all
Pages 525-540 | Received 29 Nov 2022, Accepted 12 Sep 2023, Published online: 29 Sep 2023

References

  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun;366(26):2443–2454. doi: 10.1056/NEJMoa1200690
  • Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr;32(10):1020–1030. doi: 10.1200/JCO.2013.53.0105
  • Emens LA, Kok M, Ojalvo LS. Targeting the programmed cell death-1 pathway in breast and ovarian cancer. Curr Opin Obstet Gynecol. 2016 Apr;28(2):142–147. doi: 10.1097/GCO.0000000000000257
  • Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase ib KEYNOTE-012 study. J Clin Oncol. 2016 Jul;34(21):2460–2467. doi: 10.1200/JCO.2015.64.8931
  • Pellegrino B, Tommasi C, Cursio OE, et al. A review of immune checkpoint blockade in breast cancer. Semin Oncol. 2021 Jun;48(3):208–225. doi: 10.1053/j.seminoncol.2021.09.002
  • Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810–821. doi: 10.1056/NEJMoa1910549
  • Noman MZ, Parpal S, Van Moer K, et al. Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy. Sci Adv. 2020 May;6(18):eaax7881. doi: 10.1126/sciadv.aax7881
  • Yum S, Li M, Fang Y, et al. TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections. Proc Natl Acad Sci U S A. 2021 Apr;118(14). doi: 10.1073/pnas.2100225118
  • Brown MC, Mosaheb MM, Mohme M, et al. Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling. Nat Commun. 2021 03;12(1):1858. doi: 10.1038/s41467-021-22088-1
  • Brockwell NK, Owen KL, Zanker D, et al. Neoadjuvant interferons: critical for effective PD-1-Based immunotherapy in TNBC. Cancer Immunol Res. 2017 Oct;5(10):871–884. doi: 10.1158/2326-6066.CIR-17-0150
  • Sheng W, Liu Y, Chakraborty D, et al. Simultaneous inhibition of LSD1 and TGFβ enables eradication of poorly immunogenic tumors with anti-PD-1 treatment. Cancer Discov. 2021 08;11(8):1970–1981. doi: 10.1158/2159-8290.CD-20-0017
  • Sheng W, LaFleur MW, Nguyen TH, et al. LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell. 2018 June 26;174(3):549–563.e19. doi: 10.1016/j.cell.2018.05.052
  • Le Naour J, Zitvogel L, Galluzzi L, et al. Trial watch: STING agonists in cancer therapy. Oncoimmunology. 2020 06;9(1):1777624. doi: 10.1080/2162402X.2020.1777624
  • Chin EN, Yu C, Vartabedian VF, et al. Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020 Aug;369(6506):993–999. doi: 10.1126/science.abb4255
  • Pan BS, Perera SA, Piesvaux JA, et al. An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020 08;369(6506). 10.1126/science.aba6098
  • Elion DL, Jacobson ME, Hicks DJ, et al. Therapeutically active RIG-I agonist induces immunogenic tumor cell killing in breast cancers. Cancer Res. 2018 Nov 01;78(21):6183–6195. doi: 10.1158/0008-5472.CAN-18-0730
  • Zhang C, Shang G, Gui X, et al. Structural basis of STING binding with and phosphorylation by TBK1. Nature. 2019 03;567(7748):394–398. doi: 10.1038/s41586-019-1000-2
  • Hou F, Sun L, Zheng H, et al. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011 Aug;146(3):448–461. doi: 10.1016/j.cell.2011.06.041
  • Ikeda F, Hecker CM, Rozenknop A, et al. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. EMBO J. 2007 Jul;26(14):3451–3462. doi: 10.1038/sj.emboj.7601773
  • Lin R, Heylbroeck C, Genin P, et al. Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol Cell Biol. 1999 Feb;19(2):959–966. doi: 10.1128/MCB.19.2.959
  • Kitajima S, Ivanova E, Guo S, et al. Suppression of STING associated with LKB1 loss in KRAS-Driven lung cancer. Cancer Discov. 2019 01;9(1):34–45. doi: 10.1158/2159-8290.CD-18-0689
  • Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions. Cell Death Differ. 2020 Jan;27(3):858–871. doi: 10.1038/s41418-019-0480-9
  • Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019 01;176(1–2):11–42. doi: 10.1016/j.cell.2018.09.048
  • Zachari M, Gudmundsson SR, Li Z, et al. Selective autophagy of mitochondria on a ubiquitin-Endoplasmic-reticulum platform. Dev Cell. 2020 Oct;55(2):251. doi: 10.1016/j.devcel.2020.10.002
  • Kirkin V, Rogov VV. A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell. 2019 10;76(2):268–285. doi: 10.1016/j.molcel.2019.09.005
  • Ravenhill BJ, Boyle KB, von Muhlinen N, et al. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. Mol Cell. 2019 Feb;74(2):320–329.e6. doi: 10.1016/j.molcel.2019.01.041
  • Turco E, Witt M, Abert C, et al. FIP200 Claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol Cell. 2019 04;74(2):330–346.e11. doi: 10.1016/j.molcel.2019.01.035
  • Vargas JNS, Wang C, Bunker E, et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell. 2019 Mar;74(2):347–362.e6. doi: 10.1016/j.molcel.2019.02.010
  • Wang C, Haas MA, Yang F, et al. Autophagic lipid metabolism sustains mTORC1 activity in TSC-deficient neural stem cells. Nat Metab. 2019;1(11):1127–1140. doi: 10.1038/s42255-019-0137-5
  • Yeo SK, Wang C, Guan JL. Role of FIP200 in inflammatory processes beyond its canonical autophagy function. Biochem Soc Trans. 2020 08;48(4):1599–1607. doi: 10.1042/BST20191156
  • Chen S, Wang C, Yeo S, et al. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model. Genes Dev. 2016 Apr;30(7):856–869. doi: 10.1101/gad.276428.115
  • Ganley IG, dH L, Wang J, et al. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009 May;284(18):12297–12305. doi: 10.1074/jbc.M900573200
  • Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009 Apr;20(7):1992–2003. doi: 10.1091/mbc.e08-12-1249
  • Hara T, Takamura A, Kishi C, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Bio. 2008 May;181(3):497–510. doi: 10.1083/jcb.200712064
  • Ohnstad AE, Delgado JM, North BJ, et al. Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy. EMBO J. 2020 12;39(24):e104948. doi: 10.15252/embj.2020104948
  • Turco E, Savova A, Gere F, et al. Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Nat Commun. 2021 Sep 01;12(1):5212. doi: 10.1038/s41467-021-25572-w
  • Smith MD, Harley ME, Kemp AJ, et al. CCPG1 is a non-canonical autophagy cargo receptor essential for ER-Phagy and pancreatic ER proteostasis. Dev Cell. 2018 01;44(2):217–232.e11. doi: 10.1016/j.devcel.2017.11.024
  • Zhou Z, Liu J, Fu T, et al. Phosphorylation regulates the binding of autophagy receptors to FIP200 claw domain for selective autophagy initiation. Nat Commun. 2021 March 10;12(1):1570. doi: 10.1038/s41467-021-21874-1
  • Okamoto T, Yeo SK, Hao M, et al. FIP200 suppresses immune checkpoint therapy responses in breast cancers by limiting AZI2/TBK1/IRF signaling independent of its canonical autophagy function. Cancer Res. 2020;80(17):3580–3592. doi: 10.1158/0008-5472.CAN-20-0519
  • Matsumoto G, Shimogori T, Hattori N, et al. TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation. Hum Mol Genet. 2015 Aug;24(15):4429–4442. doi: 10.1093/hmg/ddv179
  • Richter B, Sliter DA, Herhaus L, et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4039–4044. doi: 10.1073/pnas.1523926113
  • Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015 Aug 20;524(7565):309–314. doi: 10.1038/nature14893
  • Padman BS, Nguyen TN, Uoselis L, et al. LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy. Nat Commun. 2019 01;10(1):408. doi: 10.1038/s41467-019-08335-6
  • Nguyen TN, Padman BS, Usher J, et al. Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J Cell Bio. 2016 Dec;215(6):857–874. doi: 10.1083/jcb.201607039
  • Goodwin JM, Dowdle WE, DeJesus R, et al. Autophagy-independent lysosomal targeting regulated by ULK1/2-FIP200 and ATG9. Cell Rep. 2017 Sep;20(10):2341–2356. doi: 10.1016/j.celrep.2017.08.034
  • Schlütermann D, Berleth N, Deitersen J, et al. FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates. Sci Rep. 2021 July 05;11(1):13863. doi: 10.1038/s41598-021-92408-4
  • Jin S, Tian S, Luo M, et al. Tetherin suppresses type I interferon signaling by targeting MAVS for NDP52-mediated selective autophagic degradation in human cells. Mol Cell. 2017 Oct;68(2):308–322.e4. doi: 10.1016/j.molcel.2017.09.005
  • Prabakaran T, Bodda C, Krapp C, et al. Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1. EMBO J. 2018 04;37(8). 10.15252/embj.201797858
  • Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017 Jan;45(D1):D362–D368. doi: 10.1093/nar/gkw937
  • Wei H, Wang C, Groce C, et al. p62/SQSTM1 synergizes with autophagy for tumor growth in vivo. Genes Dev. 2014;28:1204–1216. doi: 10.1101/gad.237354.113
  • Liu S, Cai X, Wu J, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015 Mar 13;347(6227):aaa2630. doi: 10.1126/science.aaa2630
  • Tanaka Y, Chen ZJ. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci Signal. 2012 Mar;5(214):ra20. doi: 10.1126/scisignal.2002521
  • Saikruang W, Ang Yan Ping L, Abe H, et al. The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter. Sci Rep. 2022 March 10;12(1):3967. doi: 10.1038/s41598-022-07876-z
  • Schröder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008 Aug 6;27(15):2147–2157. doi: 10.1038/emboj.2008.143
  • Soulat D, Bürckstümmer T, Westermayer S, et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J. 2008 Aug 6;27(15):2135–2146. doi: 10.1038/emboj.2008.126
  • Gu L, Fullam A, Brennan R, et al. Human DEAD box helicase 3 couples IκB kinase ε to interferon regulatory factor 3 activation. Mol Cell Biol. 2013 May;33(10):2004–2015. doi: 10.1128/MCB.01603-12
  • McAfee Q, Zhang Z, Samanta A, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May;109(21):8253–8258. doi: 10.1073/pnas.1118193109
  • Wei H, Wei S, Gan B, et al. Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev. 2011 Jul 15;25(14):1510–1527. doi: 10.1101/gad.2051011
  • Dangaj D, Bruand M, Grimm AJ, et al. Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors. Cancer Cell. 2019 June 10;35(6):885–900.e10. doi: 10.1016/j.ccell.2019.05.004
  • Győrffy B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J. 2021;19:4101–4109. doi: 10.1016/j.csbj.2021.07.014.
  • Onomoto K, Yoneyama M, Fung G, et al. Antiviral innate immunity and stress granule responses. Trends Immunol. 2014 Sep;35(9):420–428. doi: 10.1016/j.it.2014.07.006
  • Huang J, Brumell JH. Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol. 2014 Feb;12(2):101–114. doi: 10.1038/nrmicro3160
  • Zhang Y, Sun H, Pei R, et al. The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes. Cell Discov. 2021 May 4;7(1):31. doi: 10.1038/s41421-021-00268-z
  • Hayn M, Hirschenberger M, Koepke L, et al. Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities. Cell Rep. 2021 May 18;35(7):109126. doi: 10.1016/j.celrep.2021.109126
  • Fu T, Zhang M, Zhou Z, et al. Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52. Sci Adv. 2021 Aug;7(33). doi: 10.1126/sciadv.abi6582
  • Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011 Feb;13(2):132–141. doi: 10.1038/ncb2152
  • Mathew R, Khor S, Hackett SR, et al. Functional role of autophagy-mediated proteome remodeling in cell survival signaling and innate immunity. Mol Cell. 2014 Sep;55(6):916–930. doi: 10.1016/j.molcel.2014.07.019
  • Sharma G, Ojha R, Noguera-Ortega E, et al. PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma. JCI Insight. 2020 Sep;5(17). doi: 10.1172/jci.insight.133225
  • Poillet-Perez L, Sharp DW, Yang Y, et al. Autophagy promotes growth of tumors with high mutational burden by inhibiting a T-cell immune response. Nat Cancer. 2020 09;1(9):923–934. doi: 10.1038/s43018-020-00110-7
  • Yamamoto K, Venida A, Yano J, et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 2020 05;581(7806):100–105. doi: 10.1038/s41586-020-2229-5
  • Young TM, Reyes C, Pasnikowski E, et al. Autophagy protects tumors from T cell-mediated cytotoxicity via inhibition of TNFα-induced apoptosis. Sci Immunol. 2020 12;5(54). 10.1126/sciimmunol.abb9561
  • Rebecca VW, Nicastri MC, Fennelly C, et al. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov. 2019 02;9(2):220–229. doi: 10.1158/2159-8290.CD-18-0706
  • Chen Q, Shao X, Hao M, et al. Quantitative analysis of interactive behavior of mitochondria and lysosomes using structured illumination microscopy. Biomaterials. 2020 08;250:120059. doi: 10.1016/j.biomaterials.2020.120059
  • Yeo SK, Paul R, Haas M, et al. Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer. Autophagy. 2018;14(7):1214–1225. doi: 10.1080/15548627.2018.1460010
  • Yeo SK, Wen J, Chen S, et al. Autophagy Differentially Regulates distinct breast cancer Stem-like cells in murine models via EGFR/Stat3 and Tgfβ/Smad signaling. Cancer Res. 2016 Jun;76(11):3397–3410. doi: 10.1158/0008-5472.CAN-15-2946