Adaptive mechanoproperties characterize glioblastoma fitness for invasion
Adaptive mechanoproperties characterize glioblastoma fitness for invasion
Abstract Glioblastoma are heterogeneous tumors composed of highly invasive and highly proliferative clones. Heterogeneity in invasiveness could emerge from discrete biophysical properties linked to specific molecular expression. We identified clones of patient-derived glioma propagating cells that were either highly proliferative or highly invasive and compared their cellular architecture, migratory and biophysical properties. We discovered that invasiveness was linked to cellular fitness. The most invasive cells were stiffer, developed higher mechanical forces on the substrate and moved stochastically. The mechanochemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 ectopic expression in less invasive clones increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice, counteracting microtubule bundling and promoting a robust cell-body cohesion leading to highly invasive hurdling motility. One Sentence SummaryFMN1 increases cell mechanics and invasiveness.
Monzo Pascale、Crestani Michele、Ghisleni Andrea、Maiuri Paolo、Balland Martial、Gauthier Nils C.、Tang Carol、Chong Yuk Kien、Hennig Katharina、Ang Beng Ti、Li Qingsen、Sheetz Michael P.、Richichi Cristina、Pelicci Giuliana
IFOM - the Firc Institute of Molecular OncologyIFOM - the Firc Institute of Molecular OncologyIFOM - the Firc Institute of Molecular OncologyIFOM - the Firc Institute of Molecular OncologyUniversit¨| Grenoble Alpes||CNRS UMR 5588 LIPhyIFOM - the Firc Institute of Molecular OncologyNeuro-Oncology Research Laboratory, Department of Research, National Neuroscience Institute||Duke-National University of Singapore Medical School||Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre||School of Biological Sciences, Nanyang Technological UniversityNeuro-Oncology Research Laboratory, Department of Research, National Neuroscience InstituteUniversit¨| Grenoble Alpes||CNRS UMR 5588 LIPhySingapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR)||Department of Neurosurgery, National Neuroscience Institute||Duke-National University of Singapore Medical School||Department of Physiology, Yong Loo Lin School of Medicine, National University of SingaporeIFOM - the Firc Institute of Molecular OncologyDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch||Mechanobiology Institute, National University of SingaporeDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCSDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS||Department of Translational Medicine, Piemonte Orientale University ?°Amedeo Avogadro,?±
肿瘤学神经病学、精神病学生物物理学
Monzo Pascale,Crestani Michele,Ghisleni Andrea,Maiuri Paolo,Balland Martial,Gauthier Nils C.,Tang Carol,Chong Yuk Kien,Hennig Katharina,Ang Beng Ti,Li Qingsen,Sheetz Michael P.,Richichi Cristina,Pelicci Giuliana.Adaptive mechanoproperties characterize glioblastoma fitness for invasion[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/2020.06.17.156406.点此复制
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