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GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma

Oncogene volume 42, pages 2297–2314 (2023)Cite this article

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest forms of human malignancy that currently lacks approved targeted therapeutics. Accumulating evidence suggests that SOX2 overexpression is a key driving factor for ESCC and various squamous cell carcinoma. Here, through screening a small-molecule kinase inhibitor library, we identified GSK3β as a kinase that is critically required for robust SOX2 expression in ESCC cells. GSK3β did not promote SOX2 transcriptionally but was required for SOX2 protein stability. We demonstrated that GSK3β interacts with and phosphorylates SOX2 at residue S251, which blocks SOX2 from ubiquitination and proteasome-dependent degradation instigated by ubiquitin E3 ligase CUL4ADET1-COP1. Pharmacological inhibition or knockdown of GSK3β by RNA interference selectively impaired SOX2-positive ESCC cell proliferation, cancer stemness, and tumor growth in mouse xenograft model, suggesting that GSK3β promotes ESCC tumorigenesis primarily by driving SOX2 overexpression. GSK3β was found to be frequently overexpressed in clinical esophageal tumors, and there was a positive correlation between GSK3β and SOX2 protein levels. Notably, we found that SOX2 enhanced GSK3β expression transcriptionally, suggesting the existence of a vicious cycle that drives a coordinated GSK3β and SOX2 overexpression in ESCC cells. Finally, we demonstrated in tumor xenograft model that GSK3β inhibitor AR-A014418 was effective in suppressing SOX2-positive ESCC tumor progression and inhibited tumor progression cooperatively with chemotherapeutic agent carboplatin. In conclusion, we uncovered a novel role for GSK3β in driving SOX2 overexpression and tumorigenesis and provided evidence that targeting GSK3β may hold promise for the treatment of recalcitrant ESCCs.

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Fig. 1: Identification and characterization of GSK3β inhibitors as compounds down-regulating SOX2 stability.
Fig. 2: GSK3β promotes SOX2 overexpression by promoting SOX2 protein stability.
Fig. 3: GSK3β stabilizes SOX2 by phosphorylating SOX2 at S251.
Fig. 4: S251 phosphorylation by GSK3β inhibits SOX2 ubiquitination and degradation mediated by CUL4ADET1-COP1.
Fig. 5: GSK3β is required for SOX2-positive ESCC cell proliferation and cancer stemness.
Fig. 6: SOX2 and GSK3β are co-overexpressed in ESCC tumors.
Fig. 7: Suppression of SOX2-positive ESCC tumor progression in mouse xenograft model by targeting GSK3β.

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All data generated or analyzed during this study are included in this published article [and its supplementary information files].

References

  1. Lim RZM, Mahendran HA. Malaysian upper gastrointestinal surgical S. Esophageal squamous cell carcinoma and adenocarcinoma in Malaysia - Pooled data from upper gastrointestinal centers in a multiethnic Asian population. Cancer Epidemiol. 2022;80:102211.

    Article  PubMed  Google Scholar 

  2. Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, et al. The global landscape of Esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology. 2022;163:649–658.e642.

    Article  PubMed  Google Scholar 

  3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  4. Reichenbach ZW, Murray MG, Saxena R, Farkas D, Karassik EG, Klochkova A, et al. Clinical and translational advances in esophageal squamous cell carcinoma. Adv Cancer Res. 2019;144:95–135.

    Article  CAS  PubMed  Google Scholar 

  5. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 2007;9:625–35.

    Article  CAS  PubMed  Google Scholar 

  6. Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell. 2013;12:15–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  8. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang SZ, Xiong XF, Sun Y. Functional characterization of SOX2 as an anticancer target. Signal Transduct Tar. 2020;5:135.

    Article  CAS  Google Scholar 

  10. Arnold K, Sarkar A, Yram MA, Polo JM, Bronson R, Sengupta S, et al. Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell. 2011;9:317–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003;17:126–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Graham V, Khudyakov J, Ellis P, Pevny L. SOX2 functions to maintain neural progenitor identity. Neuron. 2003;39:749–65.

    Article  CAS  Google Scholar 

  13. Bass AJ, Watanabe H, Mermel CH, Yu S, Perner S, Verhaak RG, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 2009;41:1238–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Maier S, Wilbertz T, Braun M, Scheble V, Reischl M, Mikut R, et al. SOX2 amplification is a common event in squamous cell carcinomas of different organ sites. Hum Pathol. 2011;42:1078–88.

    Article  CAS  PubMed  Google Scholar 

  15. Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature. 2014;511:246–50.

    Article  CAS  PubMed  Google Scholar 

  16. Ferone G, Song JY, Sutherland KD, Bhaskaran R, Monkhorst K, Lambooij JP, et al. SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin. Cancer Cell. 2016;30:519–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu Z, Zhou J, Zhang X, Zhang Z, Xie Y, Liu JB, et al. Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nat Genet. 2021;53:881–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M, et al. Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell. 2013;13:433–45.

    Article  CAS  PubMed  Google Scholar 

  19. Porter L, McCaughan F. SOX2 and squamous cancers. Semin Cancer Biol. 2020;67:154–67.

    Article  CAS  PubMed  Google Scholar 

  20. Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med. 2014;3:19.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cancer Genome Atlas Research N, Analysis Working Group: Asan U, Agency BCC, Brigham, Women’s H, Broad I. et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–75.

    Article  Google Scholar 

  22. Cui Y, Chen H, Xi R, Cui H, Zhao Y, Xu E, et al. Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma. Cell Res. 2020;30:902–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gen Y, Yasui K, Nishikawa T, Yoshikawa T. SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway. Cancer Sci. 2013;104:810–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fang L, Zhang L, Wei W, Jin X, Wang P, Tong Y, et al. A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation. Mol Cell. 2014;55:537–51.

    Article  CAS  PubMed  Google Scholar 

  25. Jeong CH, Cho YY, Kim MO, Kim SH, Cho EJ, Lee SY, et al. Phosphorylation of Sox2 cooperates in reprogramming to pluripotent stem cells. Stem Cells. 2010;28:2141–50.

    Article  CAS  PubMed  Google Scholar 

  26. Wang Z, Kang L, Zhang H, Huang Y, Fang L, Li M, et al. AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation. Oncogene. 2019;38:5250–64.

    Article  CAS  PubMed  Google Scholar 

  27. Fang X, Huang Z, Zhai K, Huang Q, Tao W, Kim L, et al. Inhibiting DNA-PK induces glioma stem cell differentiation and sensitizes glioblastoma to radiation in mice. Sci Transl Med. 2021;13:eabc7275.

    Article  CAS  PubMed  Google Scholar 

  28. Justilien V, Walsh MP, Ali SA, Thompson EA, Murray NR, Fields AP. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer Cell. 2014;25:139–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lv XX, Zheng XY, Yu JJ, Ma HR, Hua C, Gao RT. EGFR enhances the stemness and progression of oral cancer through inhibiting autophagic degradation of SOX2. Cancer Med. 2020;9:1131–40.

    Article  CAS  PubMed  Google Scholar 

  30. Pietrobono S, Morandi A, Gagliardi S, Gerlini G, Borgognoni L, Chiarugi P, et al. Down-regulation of SOX2 underlies the inhibitory effects of the triphenylmethane gentian violet on melanoma cell self-renewal and survival. J Invest Dermatol. 2016;136:2059–69.

    Article  CAS  PubMed  Google Scholar 

  31. Quan MY, Guo Q, Liu J, Yang R, Bai J, Wang W, et al. An FGFR/AKT/SOX2 signaling axis controls pancreatic cancer stemness. Front Cell Dev Biol. 2020;8:287.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Singh S, Trevino J, Bora-Singhal N, Coppola D, Haura E, Altiok S, et al. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Mol Cancer. 2012;11:73.

    Article  PubMed Central  Google Scholar 

  33. Wang KX, Ji WX, Yu YF, Li ZM, Niu XM, Xia WL, et al. FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer. Oncogene. 2018;37:5340–54.

    Article  CAS  PubMed  Google Scholar 

  34. Beurel E, Grieco SF, Jope RS. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther. 2015;148:114–31.

    Article  CAS  PubMed  Google Scholar 

  35. Duda P, Akula SM, Abrams SL, Steelman LS, Martelli AM, Cocco L, et al. Targeting GSK3 and associated signaling pathways involved in cancer. Cells-Basel. 2020;9:1110.

    Article  CAS  Google Scholar 

  36. Racaud-Sultan C, Vergnolle N. GSK3 beta, a master kinase in the regulation of adult stem cell behavior. Cells Basel. 2021;10:225.

    Article  CAS  Google Scholar 

  37. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J. 2001;359:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li VSW, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, et al. Wnt Signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245–56.

    Article  CAS  PubMed  Google Scholar 

  39. Jellusova J, Cato MH, Apgar JR, Ramezani-Rad P, Leung CR, Chen C, et al. Gsk3 is a metabolic checkpoint regulator in B cells. Nat Immunol. 2017;18:303–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Abd-Ellah A, Voogdt C, Krappmann D, Moller P, Marienfeld RB. GSK3 beta modulates NF-kappa B activation and RelB degradation through site-specific phosphorylation of BCL10. Sci Rep UK. 2018;8:1352.

    Article  Google Scholar 

  41. Gao SG, Li SG, Duan XX, Gu Z, Ma ZK, Yuan X, et al. Inhibition of glycogen synthase kinase 3 beta (GSK3) suppresses the progression of esophageal squamous cell carcinoma by modifying STAT3 activity. Mol Carcinogen. 2017;56:2301–16.

    Article  CAS  Google Scholar 

  42. Zhou AD, Lin KY, Zhang SC, Chen YH, Zhang N, Xue JF, et al. Nuclear GSK3 beta promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22. Nature Cell Biology. 2016;18:954–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. beta-catenin is a target for the ubiquitin-proteasome pathway. Faseb J. 1997;11:A1409–A1409.

    Google Scholar 

  44. Chen J, Ge X, Zhang W, Ding P, Du Y, Wang Q, et al. PI3K/AKT inhibition reverses R-CHOP resistance by destabilizing SOX2 in diffuse large B cell lymphoma. Theranostics. 2020;10:3151–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Nagy Z, Comer S, Smolenski A. Analysis of protein phosphorylation using phos-tag gels. Curr Protoc Protein Sci. 2018;93:e64.

    Article  PubMed  Google Scholar 

  46. Cesaro L, Pinna LA. The generation of phosphoserine stretches in phosphoproteins: mechanism and significance. Mol Biosyst. 2015;11:2666–79.

    Article  CAS  PubMed  Google Scholar 

  47. Zhou J, Tien AC, Alberta JA, Ficarro SB, Griveau A, Sun Y, et al. A sequentially priming phosphorylation cascade activates the gliomagenic transcription factor Olig2. Cell Rep. 2017;18:3167–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cui CP, Zhang Y, Wang C, Yuan F, Li H, Yao Y, et al. Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nat Commun. 2018;9:4648.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wadhwa P, Jain P, Jadhav HR. Glycogen synthase kinase 3 (GSK3): its role and inhibitors. Curr Top Med Chem. 2020;20:1522–34.

    Article  CAS  PubMed  Google Scholar 

  50. Chung JH, Jung HR, Jung AR, Lee YC, Kong M, Lee JS, et al. SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma. Sci Rep. 2018;8:1677.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Luo Q, Wu X, Chang W, Zhao P, Nan Y, Zhu X, et al. ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb/E2F1/c-Myc-mediated cancer stemness. Cell Death Differ. 2020;27:1981–97.

    Article  CAS  PubMed  Google Scholar 

  52. Gould TD, Manji HK. Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology. 2005;30:1223–37.

    Article  CAS  PubMed  Google Scholar 

  53. Hagey DW, Muhr J. Sox2 acts in a dose-dependent fashion to regulate proliferation of cortical progenitors. Cell Rep. 2014;9:1908–20.

    Article  CAS  PubMed  Google Scholar 

  54. Herreros-Villanueva M, Zhang JS, Koenig A, Abel EV, Smyrk TC, Bamlet WR, et al. SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis. 2013;2:e61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Van Hoof D, Munoz J, Braam SR, Pinkse MW, Linding R, Heck AJ, et al. Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell. 2009;5:214–26.

    Article  PubMed  Google Scholar 

  56. Gao F, Kwon SW, Zhao Y, Jin Y. PARP1 poly(ADP-ribosyl)ates Sox2 to control Sox2 protein levels and FGF4 expression during embryonic stem cell differentiation. J Biol Chem. 2009;284:22263–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Huang Y, Duan X, Wang Z, Sun Y, Guan Q, Kang L, et al. An acetylation-enhanced interaction between transcription factor Sox2 and the steroid receptor coactivators facilitates Sox2 transcriptional activity and function. J Biol Chem. 2021;297:101389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang H, Ma Y, Gu J, Liao B, Li J, Wong J, et al. Reprogramming of somatic cells via TAT-mediated protein transduction of recombinant factors. Biomaterials. 2012;33:5047–55.

    Article  CAS  PubMed  Google Scholar 

  59. Gupta N, Gopal K, Wu CS, Alshareef A, Chow A, Wu F, et al. Phosphorylation of Sox2 at threonine 116 is a potential marker to identify a subset of breast cancer cells with high tumorigenecity and stem-like features. Cancers. 2018;10:41.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Qin X, Zheng C, Yates JR 3rd, Liao L. Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins. Mol Biosyst. 2014;10:1719–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang Q, Qi S, Xu M, Yu L, Tao Y, Deng Z, et al. Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b. Cell Res. 2013;23:225–41.

    Article  CAS  PubMed  Google Scholar 

  62. Liu W, Xie L, He YH, Wu ZY, Liu LX, Bai XF, et al. Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting. Nat Commun. 2021;12:4961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Huang W, Hennrick K, Drew S. A colorful future of quantitative pathology: validation of Vectra technology using chromogenic multiplexed immunohistochemistry and prostate tissue microarrays. Hum Pathol. 2013;44:29–38.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all the other members of the J.W laboratory for their suggestions and technical assistance. We are grateful to Prof. Cheng-Ming Chiang (UT Southwestern Medical Center) for critical reading our manuscript. This study was supported by grants from National Natural Science Foundation of China (81530078 and 31961133009 to JW and 82203355 to LK), and Shanghai Science and Technology Committee (20JC1411500 to JW).

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  1. These authors contributed equally: Li Kang, Yujie Liu, Jianzhong He.

Authors and Affiliations

  1. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

    Li Kang, Yaling Wang, Xin Wu, Yunpeng Zhang, Jialun Li, Wei Wei, Jiwen Li, Lujian Liao & Jiemin Wong

  2. Joint Center for Translational Medicine, Fengxian District Central Hospital, 6600th Nanfeng Road, Fengxian District, Shanghai, China

    Li Kang & Jiemin Wong

  3. Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China

    Yujie Liu & Jianru Xiao

  4. Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Basic Medical Science, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China

    Jianzhong He, Manyu Chu & Liyan Xu

  5. The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China

    Mengyang Xue

  6. Department of Obstetrics and Gynecology, Fengxian Central Hospital affiliated to the Southern Medical University, Shanghai, China

    Mengyang Xue & Rong Zhang

  7. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

    Zhen Wang

  8. Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, China

    Enmin Li

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Contributions

KL: Conceptualization, formal analysis, investigation, visualization, methodology, writing–original draft. YL: Conceptualization, formal analysis, validation, investigation, visualization. JH: Conceptualization, validation, investigation, visualization. YW: Validation, investigation, visualization. MX: Validation, investigation, visualization. XW: Investigation. ZW: Investigation, methodology. YZ: Investigation, visualization, methodology. MC: Validation, visualization. JL: Validation, methodology. WW: Methodology. LL: Supervision, methodology. JL: Project management. EL: funding acquisition, supervision. RZ: Conceptualization, supervision, funding acquisition, project administration. LX: Conceptualization, formal analysis, supervision, funding acquisition, writing–original draft, project administration. JW: Conceptualization, formal analysis, supervision, funding acquisition, writing–original draft, project administration.

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Correspondence to Liyan Xu or Jiemin Wong.

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Kang, L., Liu, Y., He, J. et al. GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma. Oncogene 42, 2297–2314 (2023). https://doi.org/10.1038/s41388-023-02748-w

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