Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion
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 eithe...
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sg-ntu-dr.10356-1603232022-07-19T05:37:53Z Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion Monzo, Pascale Crestani, Michele Chong, Yuk Kien Ghisleni, Andrea Hennig, Katharina Li, Qingsen Kakogiannos, Nikolaos Giannotta, Monica Richichi, Cristina Dini, Tania Dejana, Elisabetta Maiuri, Paolo Balland, Martial Sheetz, Michael P. Pelicci, Giuliana Ang, Beng Ti Tang, Carol Gauthier, Nils C. School of Biological Sciences Science::Biological sciences Glioma-Cell Migration Brain-Tumor 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 mechano-chemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 expression was also linked to motility in other cancer and normal cell lines, and its ectopic expression increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice and promotes a robust mechanical cohesion, leading to highly invasive motility. Ministry of Health (MOH) this work was supported by: IFOM (starting package); the Mechanobiology Institute of Singapore (grant WBSR714-016-007 -271); the Italian Association for Cancer Research (AIRC) (Investigator Grant [IG] 20716 to N.C.G. and doctoral fellowship 3-year fellowship "MilanoMarathon-oggicorroperAIRC" -Rif. 22461 to M.C.); Marie Sklodowska-Curie actions (H2O20 -MSCA individual fellowship 796547 to A.G.); and the Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research (TCR) Flagship Programme-Tier 1(NMRC/TCR/016-NNI/2016) to C.T. 2022-07-19T05:37:53Z 2022-07-19T05:37:53Z 2021 Journal Article Monzo, P., Crestani, M., Chong, Y. K., Ghisleni, A., Hennig, K., Li, Q., Kakogiannos, N., Giannotta, M., Richichi, C., Dini, T., Dejana, E., Maiuri, P., Balland, M., Sheetz, M. P., Pelicci, G., Ang, B. T., Tang, C. & Gauthier, N. C. (2021). Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion. Developmental Cell, 56(20), 2841-2855.e8. https://dx.doi.org/10.1016/j.devcel.2021.09.007 1534-5807 https://hdl.handle.net/10356/160323 10.1016/j.devcel.2021.09.007 34559979 2-s2.0-85121014603 20 56 2841 2855.e8 en WBSR714-016-007-271 NMRC/TCR/016-NNI/2016 Developmental Cell © 2021 Elsevier Inc. All rights reserved. |
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Science::Biological sciences Glioma-Cell Migration Brain-Tumor Monzo, Pascale Crestani, Michele Chong, Yuk Kien Ghisleni, Andrea Hennig, Katharina Li, Qingsen Kakogiannos, Nikolaos Giannotta, Monica Richichi, Cristina Dini, Tania Dejana, Elisabetta Maiuri, Paolo Balland, Martial Sheetz, Michael P. Pelicci, Giuliana Ang, Beng Ti Tang, Carol Gauthier, Nils C. Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
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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 mechano-chemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 expression was also linked to motility in other cancer and normal cell lines, and its ectopic expression increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice and promotes a robust mechanical cohesion, leading to highly invasive motility. |
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School of Biological Sciences |
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School of Biological Sciences Monzo, Pascale Crestani, Michele Chong, Yuk Kien Ghisleni, Andrea Hennig, Katharina Li, Qingsen Kakogiannos, Nikolaos Giannotta, Monica Richichi, Cristina Dini, Tania Dejana, Elisabetta Maiuri, Paolo Balland, Martial Sheetz, Michael P. Pelicci, Giuliana Ang, Beng Ti Tang, Carol Gauthier, Nils C. |
format |
Article |
author |
Monzo, Pascale Crestani, Michele Chong, Yuk Kien Ghisleni, Andrea Hennig, Katharina Li, Qingsen Kakogiannos, Nikolaos Giannotta, Monica Richichi, Cristina Dini, Tania Dejana, Elisabetta Maiuri, Paolo Balland, Martial Sheetz, Michael P. Pelicci, Giuliana Ang, Beng Ti Tang, Carol Gauthier, Nils C. |
author_sort |
Monzo, Pascale |
title |
Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
title_short |
Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
title_full |
Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
title_fullStr |
Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
title_full_unstemmed |
Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion |
title_sort |
adaptive mechanoproperties mediated by the formin fmn1 characterize glioblastoma fitness for invasion |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/160323 |
_version_ |
1739837413668159488 |