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Lrig1 regulates the balance between proliferation and quiescence in glioblastoma stem cells
dc.contributor.author | Ferguson, Kirsty | |
dc.contributor.author | Blin, Carla | |
dc.contributor.author | Alfazema, Neza | |
dc.contributor.author | Gangoso, Ester | |
dc.contributor.author | Pollard, Steven | |
dc.contributor.author | Marques-Torrejon, Maria Angeles | |
dc.date.accessioned | 2023-01-25T18:01:34Z | |
dc.date.available | 2023-01-25T18:01:34Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Ferguson KM, Blin C, Alfazema N, Gangoso E, Pollard SM and Marques-Torrejon MA (2022), Lrig1 regulates the balance between proliferation and quiescence in glioblastoma stem cells. Front. Cell Dev. Biol. 10:983097. doi: 10.3389/fcell.2022.983097 | ca_CA |
dc.identifier.issn | 2296-634X | |
dc.identifier.uri | http://hdl.handle.net/10234/201434 | |
dc.description.abstract | Patients with glioblastoma (GBM) face a dismal prognosis. GBMs are driven by glioblastoma stem cells (GSCs) that display a neural stem cell (NSC)-like phenotype. These glioblastoma stem cells are often in a quiescent state that evades current therapies, namely debulking surgery and chemo/radiotherapy. Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signalling across many tissue stem cells. Lrig1 is highly expressed in gliomas and importantly, polymorphisms have been identified that are risk alleles for patients with GBM, which suggests some functional role in gliomagenesis. We previously reported that Lrig1 is a gatekeeper of quiescence exit in adult mouse neural stem cells, suppressing epidermal growth factor receptor signalling prior to cell cycle re-entry. Here, we perform gain- and loss-of-function studies to understand the function of Lrig1 in glioblastoma stem cells. Using a novel mouse glioblastoma stem cell model, we show that genetic ablation of Lrig1 in cultured GBM stem cells results in higher proliferation and loss of quiescence. In vivo, mice transplanted with glioblastoma stem cells lacking Lrig1 display lower survival compared to Lrig1 WT glioblastoma stem cells, with tumours displaying increased proportions of proliferative cells and reduced quiescent subpopulations. In contrast, Lrig1 overexpression in mouse glioblastoma stem cells results in enhanced quiescence and reduced proliferation, with impaired tumour formation upon orthotopic transplantation. Mechanistically, we find that Lrig1-null cells have a deficiency in BMP signalling responses that may underlie their lack of responsiveness to quiescence cues in vivo. These findings highlight important roles for Lrig1 in controlling responsiveness to both epidermal growth factor receptor and BMPR signalling, and hence the proportions of quiescent and proliferative subpopulations in GBMs. | ca_CA |
dc.format.extent | 12 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Frontiers Media | ca_CA |
dc.relation.isPartOf | Frontiers in Cell and Developmental Biology 10:983097 | ca_CA |
dc.rights | © 2022 Ferguson, Blin, Alfazema, Gangoso, Pollard and MarquesTorrejon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | ca_CA |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | ca_CA |
dc.subject | glioblastoma | ca_CA |
dc.subject | neural stem cell | ca_CA |
dc.subject | quiescence | ca_CA |
dc.subject | Lrig1 | ca_CA |
dc.subject | BMP | ca_CA |
dc.title | Lrig1 regulates the balance between proliferation and quiescence in glioblastoma stem cells | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.3389/fcell.2022.983097 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
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Gangoso, Pollard and MarquesTorrejon. This is an open-access article
distributed under the terms of the
Creative Commons Attribution License
(CC BY). The use, distribution or
reproduction in other forums is
permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original
publication in this journal is cited, in
accordance with accepted academic
practice. No use, distribution or
reproduction is permitted which does
not comply with these terms.