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Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis

Oncogene volume 42, pages 2218–2233 (2023)Cite this article

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Abstract

Neuroblastoma is a pediatric cancer that can present as low- or high-risk tumors (LR-NBs and HR-NBs), the latter group showing poor prognosis due to metastasis and strong resistance to current therapy. Whether LR-NBs and HR-NBs differ in the way they exploit the transcriptional program underlying their neural crest, sympatho-adrenal origin remains unclear. Here, we identified the transcriptional signature distinguishing LR-NBs from HR-NBs, which consists mainly of genes that belong to the core sympatho-adrenal developmental program and are associated with favorable patient prognosis and with diminished disease progression. Gain- and loss-of-function experiments revealed that the top candidate gene of this signature, Neurexophilin-1 (NXPH1), has a dual impact on NB cell behavior in vivo: whereas NXPH1 and its receptor α-NRXN1 promote NB tumor growth by stimulating cell proliferation, they conversely inhibit organotropic colonization and metastasis. As suggested by RNA-seq analyses, these effects might result from the ability of NXPH1/α-NRXN signalling to restrain the conversion of NB cells from an adrenergic state to a mesenchymal one. Our findings thus uncover a transcriptional module of the sympatho-adrenal program that opposes neuroblastoma malignancy by impeding metastasis, and pinpoint NXPH1/α-NRXN signaling as a promising target to treat HR-NBs.

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Fig. 1: Identification of the transcriptional signature discriminating LR-NB and HR-NBs.
Fig. 2: A core sympatho-adrenal signature is enriched in LR-NBs and associates with better patient prognosis.
Fig. 3: The expression of NXPH1 and its receptors α-NRXN1/2 associates with favorable patient prognosis and identifies NB cells with a neural crest stem cell identity.
Fig. 4: Inhibition of NXPH1/α-NRXN1 signaling alters the behavior of NB cells in vitro.
Fig. 5: The activity of NXPH1 and α-NRXN1 is required for NB growth.
Fig. 6: Inhibiting NXPH1/α-NRXN1 signaling increases the metastatic growth and colonizing potential of SK-N-SH cells.
Fig. 7: Reducing NXPH1 activity forces NB cells to adopt a mesenchymal state.

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All data generated or analyzed during this study are included in this paper and its supplementary information files.

References

  1. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. SEER Cancer Statistics. SEER Cancer Statistics Review. 2012.

  2. Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer 2008;112:416–32.

    Article  PubMed  Google Scholar 

  3. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tolbert VP, Coggins GE, Maris JM, Maris JM. Genetic susceptibility to neuroblastoma. Curr Opin Genet Dev. 2017;42:81–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vo KT, Matthay KK, Neuhaus J, London WB, Hero B, Ambros PF, et al. Clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: A report from the International Neuroblastoma Risk Group project. J Clin Oncol. 2014;32:3169–76.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cohn SL, Pearson ADJ, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: An INRG task force report. J Clin Oncol. 2009;27:289–97.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, et al. The International Neuroblastoma Risk Group (INRG) staging system: An INRG Task Force report. J Clin Oncol. 2009;27:298–303.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, et al. Neuroblastoma. Nat Rev Dis Prim. 2016;2:16078.

    Article  PubMed  Google Scholar 

  9. Nakagawara A, Li Y, Izumi H, Muramori K, Inada H, Nishi M. Neuroblastoma. Jpn J Clin Oncol. 2018;48:214–41.

    Article  PubMed  Google Scholar 

  10. Cheung NK, Dyer MA. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 2013;13:397–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, Van Sluis P, Volckmann R, et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet. 2015;47:1411–4.

    Article  CAS  PubMed  Google Scholar 

  12. Van Groningen T, Koster J, Valentijn LJ, Zwijnenburg DA, Akogul N, Hasselt NE, et al. Neuroblastoma is composed of two super-enhancer-associated differentiation states. Nat Genet. 2017;49:1261–6.

    Article  PubMed  Google Scholar 

  13. Boeva V, Louis-Brennetot C, Peltier A, Durand S, Pierre-Eugène C, Raynal V, et al. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries. Nat Genet. 2017;49:1408–13.

    Article  CAS  PubMed  Google Scholar 

  14. Sengupta S, Das S, Crespo AC, Cornel AM, Patel AG, Mahadevan NR, et al. Mesenchymal and adrenergic cell lineage states in neuroblastoma possess distinct immunogenic phenotypes. Nat Cancer. 2022;3:1228–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. De Preter K, Vandesompele J, Heimann P, Yigit N, Beckman S, Schramm A, et al. Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes. Genome Biol. 2006;7:R84.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dong R, Yang R, Zhan Y, Zheng S, Li K, Wang JJF, et al. Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma. Cancer Cell. 2020;38:716–733.e6.

    Article  CAS  PubMed  Google Scholar 

  17. Hanemaaijer ES, Margaritis T, Sanders K, Bos FL, Candelli T, Al-Saati H, et al. Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype. Proc Natl Acad Sci USA. 2021;118:e2022350118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jansky S, Kumar Sharma A, Körber V, Quintero A, Toprak UH, Wecht EM, et al. Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma. Nat Genet. 2021;53:683–93.

    Article  CAS  PubMed  Google Scholar 

  19. Kameneva P, Artemov AV, Eleni Kastriti M, Faure L, Olsen TK, Otte J, et al. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin. Nat Genet. 2021;53:694–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kildisiute G, Kholosy WM, Young MD, Roberts K, Elmentaite R, van Hooff SR, et al. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell. Sci Adv. 2021;7:eabd3311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bedoya-Reina OC, Li W, Arceo M, Plescher M, Bullova P, Pui H, et al. Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors. Nat Commun. 2021;12:1–15.

    Article  Google Scholar 

  22. Furlan A, Dyachuk V, Kastriti ME, Calvo-Enrique L, Abdo H, Hadjab S, et al. Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla. Science (80-). 2017;357:eaal3753.

    Article  Google Scholar 

  23. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11:1466–77.

    Article  CAS  PubMed  Google Scholar 

  24. Gómez S, Castellano G, Mayol G, Suñol M, Queiros A, Bibikova M, et al. DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights. Epigenomics 2015;7:1137–53.

    Article  PubMed  Google Scholar 

  25. Rothstein M, Simoes-Costa M. Heterodimerization of TFAP2 pioneer factors drives epigenomic remodeling during neural crest specification. Genome Res. 2020;30:35–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Martik ML, Bronner ME. Regulatory Logic Underlying Diversification of the Neural Crest. Trends Genet. 2017;33:715–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Missler M, Südhof TC. Neurexophilins form a conserved family of neuropeptide-like glycoproteins. J Neurosci. 1998;18:3630–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Petrenko AG, Ullrich B, Missler M, Krasnoperov V, Rosahl TW, Südhof TC, et al. Structure and evolution of neurexophilin. J Neurosci. 1996;16:4360–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Reissner C, Stahn J, Breuer D, Klose M, Pohlentz G, Mormann M, et al. Dystroglycan binding to α-Neurexin competes with neurexophilin-1 and neuroligin in the brain. J Biol Chem. 2014;289:27585–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Südhof TC. Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits. Cell. 2017;171:745–69.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Walton JD, Kattan DR, Thomas SK, Spengler BA, Guo HF, Biedler JL, et al. Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia 2004;6:838–45.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hansford LM, McKee AE, Zhang L, George RE, Gerstle JT, Thorner PS, et al. Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell. Cancer Res. 2007;67:11234–43.

    Article  CAS  PubMed  Google Scholar 

  33. Ikegaki N, Shimada H, Fox AM, Regan PL, Jacobs JR, Hicks SL, et al. Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas. Proc Natl Acad Sci USA. 2013;110:6097–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Takenobu H, Shimozato O, Nakamura T, Ochiai H, Yamaguchi Y, Ohira M, et al. CD133 suppresses neuroblastoma cell differentiation via signal pathway modification. Oncogene 2011;30:97–105.

    Article  CAS  PubMed  Google Scholar 

  35. Foster BM, Zaidi D, Young TR, Mobley ME, Kerr BA. CD117/c-kit in cancer stem cell-mediated progression and therapeutic resistance. Biomedicines. 2018;6:31.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004;101:14228–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jiang X, Gwye Y, McKeown SJ, Bronner-Fraser M, Lutzko C, Lawlor ER. Isolation and characterization of neural crest stem cells derived from in vitro-differentiated human embryonic stem cells. Stem Cells Dev. 2009;18:1059–70.

    Article  CAS  PubMed  Google Scholar 

  38. DuBois SG, Kalika Y, Lukens JN, Brodeur GM, Seeger RC, Atkinson JB, et al. Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol. 1999;21:181–9.

    Article  CAS  PubMed  Google Scholar 

  39. Vasaikar SV, Deshmukh AP, den Hollander P, Addanki S, Kuburich NA, Kudaravalli S, et al. EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures. Br J Cancer. 2021;124:259–69.

    Article  CAS  PubMed  Google Scholar 

  40. Ferronha T, Angeles Rabadán M, Gil-Guiñon E, Le Dréau G, de Torres C, Martí E. LMO4 is an essential cofactor in the Snail2-mediated epithelial-to-mesenchymal transition of neuroblastoma and neural crest cells. J Neurosci. 2013;33:2773–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kildisiute G, Young MD, Behjati S. Pitfalls of Applying Mouse Markers to Human Adrenal Medullary Cells. Cancer Cell. 2021;39:132–3.

    Article  CAS  PubMed  Google Scholar 

  42. Bedoya-Reina OC, Schlisio S. Chromaffin Cells with Sympathoblast Signature: Too Similar to Keep Apart? Cancer Cell. 2021;39:134–5.

    Article  CAS  PubMed  Google Scholar 

  43. Yang R, Luo W, Zhan Y, Li K, Wang J, Dong R. Response to Kildsiute et al. and Bedoya-Reina and Schlisio. Cancer Cell. 2021;39:136–7.

    Article  CAS  PubMed  Google Scholar 

  44. Kameneva P, Artemov VA, Kastriti ME, Sundström E, Kharchenko PV, Adameyko I. Evolutionary switch in expression of key markers between mouse and human leads to mis-assignment of cell types in developing adrenal medulla. Cancer Cell. 2021;39:590–1.

    Article  CAS  PubMed  Google Scholar 

  45. Warnat P, Oberthuer A, Fischer M, Westermann F, Eils R, Brors B. Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes. BMC Cancer. 2007;7:1–11.

    Article  Google Scholar 

  46. Decock A, Ongenaert M, Cannoodt R, Verniers K, De Wilde B, Laureys G, et al. Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma. Oncotarget 2016;7:1960–72.

    Article  PubMed  Google Scholar 

  47. Delloye-Bourgeois C, Bertin L, Thoinet K, Jarrosson L, Kindbeiter K, Buffet T, et al. Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma. Cancer Cell. 2017;32:427–443.e8.

    Article  CAS  PubMed  Google Scholar 

  48. Ben Amar D, Thoinet K, Villalard B, Imbaud O, Costechareyre C, Jarrosson L, et al. Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model. Nat Commun. 2022;13:2549.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Aiuti BA, Webb IJ, Bleul C, Springer T. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med. 1997;185:111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hidalgo A, Weiss LA, Frenette PS, Hidalgo A, Weiss LA, Frenette PS. Functional selectin ligands mediating human CD34(+) cell interactions with bone marrow endothelium are enhanced postnatally. J Clin Investig. 2002;110:559–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Aravindan N, Babu D, Herman TS. Significance of hematopoietic surface antigen CD34 in neuroblastoma prognosis and the genetic landscape of CD34-expressing neuroblastoma CSCs. Cell Biol Toxicol. 2021;37:461–78.

    Article  CAS  PubMed  Google Scholar 

  52. Monterrubio C, Paco S, Olaciregui NG, Pascual-Pasto G, Vila-Ubach M, Cuadrado-Vilanova M, et al. Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8. J Control Release. 2017;255:108–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zenkova D, Kamenev V, Sablina R, Artyomov M, Sergushichev A. Phantasus: visual and interactive gene expression analysis. 2018. https://doi.org/10.18129/B9.bioc.phantasus.

  54. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: Tool for the unification of biology. Nat Genet. 2000;25:25–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Carbon S, Douglass E, Dunn N, Good B, Harris NL, Lewis SE, et al. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 2019;47:D330–8.

    Article  CAS  Google Scholar 

  56. Su Z, Fang H, Hong H, Shi L, Zhang W, Zhang W, et al. An investigation of biomarkers derived from legacy microarray data for their utility in the RNA-seq era. Genome Biol. 2014;15:523.

    Article  PubMed  Google Scholar 

  57. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013;29:15–21.

    Article  CAS  PubMed  Google Scholar 

  58. Liao Y, Smyth GK, Shi W. FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014;30:923–30.

    Article  CAS  PubMed  Google Scholar 

  59. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, et al. A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen. Cell 2006;124:1283–98.

    Article  CAS  PubMed  Google Scholar 

  61. Shin KJ, Wall EA, Zavzavadjian JR, Santat LA, Liu J, Hwang JI, et al. A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Proc Natl Acad Sci USA. 2006;103:13759–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bookout AL, Cummins CL, Mangelsdorf DJ, Pesola JM, Kramer MF. High-Throughput Real-Time Quantitative Reverse Transcription PCR. Curr Protoc Mol Biol. 2006;15:15.8.

  63. Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8:511–24.

    Article  CAS  PubMed  Google Scholar 

  64. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: An open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82.

    Article  CAS  PubMed  Google Scholar 

  65. Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET, et al. ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinforma. 2017;18:529.

    Article  Google Scholar 

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Acknowledgements

We thank the members of the laboratories of E.M., Maria L. Arbonés and Sebastian Pons (IBMB-CSIC) for discussions related to this study. We thank the Xarxa de Bancs de Tumors de Catalunya (XBTC; sponsored by Pla Director d’Oncologia de Catalunya), the “Biobanc de l’Hospital Infantil Sant Joan de Déu per a la Investigació” integrated in the National Network Biobanks of ISCIII for the sample and data procurement, the IBMB Molecular Imaging platform and the PCB Flow Cytometry facility for their assistance. We are grateful to Marian Martínez-Balbás (IBMB-CSIC) and Joan Xavier Comella (Vall d’Hebron Institut de Recerca, Barcelona, Spain) for providing reagents.

Funding

This work was supported by grants from the Ministerio de Ciencia e Innovacion, Gobierno de España (MCINN; BFU2016-81887-REDT and BFU2016-77498-P) and the Asociación Española Contra el Cancer (AECC CI_2016) to EM, from the Fondo de Investigación en Salud (FIS) - Instituto de salud Carlos III (PI14/00038) and the NEN association (Association of Families and Friends of Patients with Neuroblastoma) to CL, from the Instituto de Salud Carlos III-FSE (MS17/00037; PI18/00014; PI21/00020) to TC-T, from Instituto de Salud Carlos III (CP22/00127, co-funded by European Social Fund “Investing in your future”) to BMJ, from the Agence Nationale pour la Recherche (ANR-17-CE14-0023-01, ANR-17-CE14-0009-02) and the city of Paris (Emergence program) to ELG, from ISCIII-FEDER (CP13/00189 and CPII18/00009) to AMC. LF received a PhD fellowship from the Spanish Ministry of Science, Education and Universities (FPU AP2012-2222). LT-D was funded by a FPI Fellowship (PRE2019-088005). GLD was supported by the Asociación Española Contra el Cancer (AECC #AIO14142105LED).

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Author notes

  1. Gwenvael Le Dréau

    Present address: Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France

  2. These authors contributed equally: Soledad Gómez-González, Catalina Rozalén, Iván Pérez-Núñez, Irene Sangrador, Laureano Tomás-Daza.

Authors and Affiliations

  1. Department of Cells and Tissues, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028, Barcelona, Spain

    Lucía Fanlo, Susana Usieto, Elisa Martí & Gwenvael Le Dréau

  2. SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain

    Soledad Gómez-González, Mònica Vila-Ubach, Angel M. Carcaboso & Cinzia Lavarino

  3. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), 08003, Barcelona, Spain

    Catalina Rozalén, Iván Pérez-Núñez, Irene Sangrador & Toni Celià-Terrassa

  4. Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain

    Laureano Tomás-Daza & Biola M. Javierre

  5. Institut National de la Santé et de la Recherche Médicale (Inserm, UMR_S 1166), Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France

    Emmanuel L. Gautier

  6. Molecular Imaging Platform, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028, Barcelona, Spain

    Elena Rebollo

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  1. Lucía Fanlo
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Contributions

Conceptualization: LF and GLD; Methodology: LF, SG-G, CR, IP-N, IS, LT-D, ELG, SU, ER, MV-U, and GLD; Investigation: LF, SG-G, CR, IP-N, IS, LT-D, ELG, and GLD; Resources: AMC, BMJ, TC-T, CL, and EM; Visualization: LF and GLD; Writing—Original Draft: LF and GLD; Funding Acquisition: ELG, AMC, BMJ, TC-T, CL, and EM. Supervision: EM and GLD.

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Correspondence to Gwenvael Le Dréau.

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Fanlo, L., Gómez-González, S., Rozalén, C. et al. Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis. Oncogene 42, 2218–2233 (2023). https://doi.org/10.1038/s41388-023-02742-2

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