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Amplifications of the proto-oncogene MYC display notable heterogeneity at the single-cell level and are associated with a particularly dismal prognosis in high-risk medulloblastomas (MBs). The aim of this study was to establish the relevance of interclonal cross-talk between MYC-driven and non-MYC-driven MB cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used fluorescence in situ hybridization, single-cell transcriptomics, and immunohistochemistry, in vitro isogenic cell models, non-targeted proteomics, mass spectrometry-based metabolite quantification, HUVECs tube formation assay, and orthotopic in vivo experiments to investigate interclonal cross-talk in MB.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found that the release of lactate dehydrogenase A (LDHA) from MYC-driven cells facilitates metastatic seeding and outgrowth, while secretion of dickkopf WNT signaling pathway inhibitor 3 from non-MYC-driven cells promotes tumor angiogenesis. This tumor-supporting interaction between both subclones was abrogated by targeting the secretome through pharmacological and genetic inhibition of LDHA, which significantly suppressed tumor cell migration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study reveals the functional relevance of clonal diversity and highlights the therapeutic potential of targeting the secretome to interrupt interclonal communication and progression in high-risk MB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noac068","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T12:33:33Z","timestamp":1647520413000},"page":"1509-1523","source":"Crossref","is-referenced-by-count":26,"title":["Intratumoral heterogeneity of MYC drives medulloblastoma metastasis and angiogenesis"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3442-8043","authenticated-orcid":false,"given":"Nan","family":"Qin","sequence":"first","affiliation":[{"name":"German Cancer Consortium (DKTK), Partner Site Essen\/D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich Heine University, University Hospital D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Institute of Neuropathology, Medical Faculty, HHU, UKD , Du\u0308sseldorf , Germany"}]},{"given":"Eunice","family":"Paisana","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular \u2013 Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa , Lisbon , Portugal"}]},{"given":"Maike","family":"Langini","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), Partner Site Essen\/D\u00fcsseldorf , D\u00fcsseldorf , 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D\u00fcsseldorf , Germany"},{"name":"Institute of Neuropathology, Medical Faculty, HHU, UKD , Du\u0308sseldorf , Germany"}]},{"given":"Lena","family":"Bl\u00fcmel","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), Partner Site Essen\/D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich Heine University, University Hospital D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Institute of Neuropathology, Medical Faculty, HHU, UKD , Du\u0308sseldorf , Germany"}]},{"given":"Sarah","family":"G\u00f6bbels","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), Partner Site Essen\/D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich Heine University, University Hospital D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Institute of 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