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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 hypothesised that GSCs’ morphological features affect tumour 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 sufficient and necessary for maintaining proper GSC morphology, TTC abundance and cell cycle progression as well as required for cell survival. Remarkably, both the effects on cell morphology and proliferation depend on the stability of actin cytoskeleton. Hence, cell morphology and its regulators play a key role in tumor progression by mediating cell-cell communication. We thus propose that GSC morphological heterogeneity holds the potential to identify new therapeutic targets and diagnostic markers. Overall design: Glioblastoma stem cells have been treated with ADD3 overexpression or CRISPR-Cas9 mediated knock-out to understand the role of ADD3 on cell morphology and tumour growth.</long_description><tag>xref:PubMed:39592188</tag><repository>ENA</repository><description_synonyms>grade IV adult astrocytic tumour, Malignant Neoplasm, Neoplasms, postnatal development, Benign Neoplasm, growth and development, biosynthesis, Giant Cell, Grade IV, Tumor, Astrocytomas, Malignant, development, adult glioblastoma multiforme, Benign, primary glioblastoma multiforme, Neoplasm, glioblastoma, R75380, Giant Cell Glioblastomas, multicellular organismal biosynthetic process, glioblastoma multiforme, single-organism biosynthetic process, Glioblastoma, grade IV adult astrocytic tumor, growth pattern, Malignancy, formation, spongioblastoma multiforme, non-developmental growth, anabolism, postnatal growth, Glioblastomas, GBM, Benign Neoplasms, Cancers, Giant Cell Glioblastoma, Astrocytoma, Malignant Neoplasms, synthesis, Neoplasias, Glioblastoma Multiforme, AI463285, Grade IV Astrocytomas, grade IV adult Astrocytic tumor, Malignancies, ADDL, Grade IV Astrocytoma, other neoplasm, growth, Neoplasia, Cancer, Tumors, Malignant Neoplasms.</description_synonyms><name_synonyms>grade IV adult astrocytic tumour, Malignant Neoplasm, Neoplasms, postnatal development, Benign Neoplasm, growth and development, biosynthesis, Giant Cell, Grade IV, Tumor, Astrocytomas, Malignant, development, adult glioblastoma multiforme, Benign, primary glioblastoma multiforme, Neoplasm, glioblastoma, R75380, Giant Cell Glioblastomas, multicellular organismal biosynthetic process, glioblastoma multiforme, single-organism biosynthetic process, Glioblastoma, grade IV adult astrocytic tumor, growth pattern, Malignancy, formation, spongioblastoma multiforme, non-developmental growth, anabolism, postnatal growth, Glioblastomas, GBM, Benign Neoplasms, Cancers, Giant Cell Glioblastoma, Astrocytoma, Malignant Neoplasms, synthesis, Neoplasias, Glioblastoma Multiforme, AI463285, Grade IV Astrocytomas, grade IV adult Astrocytic tumor, Malignancies, ADDL, Grade IV Astrocytoma, other neoplasm, growth, Neoplasia, Cancer, Tumors, Malignant Neoplasms.</name_synonyms></additional><is_claimable>false</is_claimable><name>Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections</name><description>Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections</description><dates><last_updated>2025-09-24</last_updated><first_public>2024-11-15</first_public></dates><accession>PRJNA1180487</accession><cross_references><GEO>GSE280761</GEO><taxon>9606</taxon><PubMed>39592188</PubMed></cross_references></HashMap>