2026-04-13T07:04:48Zhttps://recercat.cat/oai/requestoai:recercat.cat:10459.1/689002024-12-05T21:50:55Zcom_2072_3622col_2072_479130
RECERCAT
author
Alza, Lía
author
Nàger Grifo, Mireia
author
Visa Pretel, Anna
author
Cantí Nicolás, Carles
author
Herreros Danés, Judit
2024-12-05T21:50:55Z
2024-12-05T21:50:55Z
2020-06-02T10:35:09Z2020-06-02T10:35:09Z2020-04-272020-06-02T10:35:09Z
http://hdl.handle.net/10459.1/68900
Focal adhesion kinase (FAK) is a central component of focal adhesions that regulate cancer cell proliferation and migration. Here, we studied the effects of FAK inhibition in glioblastoma (GBM), a fast growing brain tumor that has a poor prognosis. Treating GBM cells with the FAK inhibitor PF-573228 induced a proliferative arrest and increased cell size. PF-573228 also reduced the growth of GBM neurospheres. These effects were associated with increased p27/CDKN1B levels and β-galactosidase activity, compatible with acquisition of senescence. Interestingly, FAK inhibition repressed the expression of the autophagy cargo receptor p62/SQSTM-1. Moreover, depleting p62 in GBM cells also induced a senescent-like phenotype through transcriptional upregulation of p27. Our results indicate that FAK inhibition arrests GBM cell proliferation, resulting in cell senescence, and pinpoint p62 as being key to this process. These findings highlight the possible therapeutic value of targeting FAK in GBM.This research was funded by Spanish Ministry of Science & Innovation (“Retos” Program), grant number RTI2018-094739-B-I00 to JH and CC. The APC was funded by Spanish Ministry of Science & Innovation
cc by (c) Alza et al., 2020 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/
FAK
Glioblastoma
Proliferation
p62/SQSTM-1
p27/CDKN1B
FAK inhibition induces glioblastoma cell senescence-like state through p62 and p27
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion