biostudies-literatureBarelli CFondazione AIRC per la ricerca sul cancro ETSe202402823https://www.ebi.ac.uk/biostudies/studies/S-EPMC11599137biostudies-literatureUnknown8(2)Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology. As GSCs closely resemble neural progenitor cells during neurodevelopment, we hypothesized that GSCs' morphological features affect tumor progression. We identified GSC morphology as a new layer of tumoral heterogeneity with important consequences on GSC proliferation. Strikingly, we showed that the neurodevelopmental morphoregulator ADD3 is sufficiLife science allianceMorphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections.PMC1159913727157Barelli CCampione AOsei IStefini RIannuzzi RMSorrentino SSokolova VIorio FFaletti SKalebic NSicuri GMKaluthantrige Don FMinotti MRVilla GBertani IfalseMorphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections.Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology. As GSCs closely resemble neural progenitor cells during neurodevelopment, we hypothesized that GSCs' morphological features affect tumor progression. We identified GSC morphology as a new layer of tumoral heterogeneity with important consequences on GSC proliferation. Strikingly, we showed that the neurodevelopmental morphoregulator ADD3 is suffici2025-01-01T00:00:00Z2025 Feb2025-04-04T02:43:55.006Z2025-04-04T02:43:55.006ZS-EPMC115991373959218810.26508/lsa.202402823