Rnd3 is a crucial mediator of the invasive phenotype of glioblastoma cells downstream of receptor tyrosine kinase signalling

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dc.contributor.author Almarán, Beatriz
dc.contributor.author Ramis, Guillem
dc.contributor.author Fernández de Mattos, Silvia
dc.contributor.author Villalonga, Priam
dc.date.accessioned 2023-03-14T08:06:03Z
dc.date.available 2023-03-14T08:06:03Z
dc.identifier.uri http://hdl.handle.net/11201/160285
dc.description.abstract [eng] Enhanced invasiveness is one of the defining biological traits of glioblastoma cells, which exhibit an infiltrative nature that severely hinders surgical resection. Among the molecular lesions responsible for GBM aggressiveness, aberrant receptor tyrosine kinase (RTK) signalling is well-characterised. Enhanced RTK signalling directly impacts a myriad of cellular pathways and downstream effectors, which include the Rho GTPase family, key regulators of actin cytoskeletal dynamics. Here, we have analysed the functional crosstalk between oncogenic signals emanating from RTKs and Rho GTPases and focused on the specific contribution of Rnd3 to the invasive phenotype of GBM in this context. We found that RTK inhibition with a panel of RTK inhibitors decreased cell motility and cell invasion and promoted dramatic actin cytoskeleton reorganisation through activation of the RhoA/Rho-associated protein kinase 1 (ROCK) axis. RTK inhibition also significantly decreased Rnd3 expression levels. Consistently, shRNA-mediated Rnd3 silencing revealed that Rnd3 depletion promoted substantial changes in the actin cytoskeleton and reduced cell motility and invasion capacity, recapitulating the effects observed upon RTK inhibition. Our results indicate that Rnd3 is a crucial mediator of RTK oncogenic signalling involved in actin cytoskeletal reorganisation, which contributes to determining the invasive phenotype of GBM cells
dc.format application/pdf
dc.relation.isformatof https://doi.org/10.3390/cells11233716
dc.relation.ispartof Cells, 2022, vol. 11, num. 23, p. 3716 (1)-3716 (17)
dc.rights , 2022
dc.subject.classification Ciències de la salut
dc.subject.classification 57 - Biologia
dc.subject.other Medical sciences
dc.subject.other 57 - Biological sciences in general
dc.title Rnd3 is a crucial mediator of the invasive phenotype of glioblastoma cells downstream of receptor tyrosine kinase signalling
dc.type info:eu-repo/semantics/article
dc.date.updated 2023-03-14T08:06:03Z
dc.subject.keywords glioblastoma
dc.subject.keywords invasión
dc.subject.keywords Rho GTPases
dc.subject.keywords Rnd3
dc.subject.keywords receptor tyrosine kinase
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.identifier.doi https://doi.org/10.3390/cells11233716

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