Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections.

Autor:	Barelli C; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Kaluthantrige Don F; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Iannuzzi RM; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Faletti S; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Bertani I; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Osei I; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Sorrentino S; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Villa G; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Sokolova V; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Campione A; https://ror.org/029gmnc79 Human Technopole, Milan, Italy.; Ospedale Nuovo di Legnano, Legnano, Italy., Minotti MR; Ospedale Nuovo di Legnano, Legnano, Italy., Sicuri GM; Ospedale Nuovo di Legnano, Legnano, Italy., Stefini R; Ospedale Nuovo di Legnano, Legnano, Italy., Iorio F; https://ror.org/029gmnc79 Human Technopole, Milan, Italy., Kalebic N; https://ror.org/029gmnc79 Human Technopole, Milan, Italy nereo.kalebic@fht.org.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Nov 26; Vol. 8 (2). Date of Electronic Publication: 2024 Nov 26 (Print Publication: 2025).
DOI:	10.26508/lsa.202402823
Abstrakt:	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 sufficient and necessary for maintaining proper GSC morphology, TTC abundance, cell cycle progression, and chemoresistance, 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. (© 2024 Barelli et al.)
Databáze:	MEDLINE
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