2026-04-17T07:40:54Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/689002024-12-05T21:50:55Zcom_2072_3622col_2072_479130

00925njm 22002777a 4500 dc Alza, Lía author Nàger Grifo, Mireia author Visa Pretel, Anna author Cantí Nicolás, Carles author Herreros Danés, Judit author 2020-06-02T10:35:09Z 2020-06-02T10:35:09Z 2020-04-27 2020-06-02T10:35:09Z 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 http://hdl.handle.net/10459.1/68900 FAK Glioblastoma Proliferation p62/SQSTM-1 p27/CDKN1B FAK inhibition induces glioblastoma cell senescence-like state through p62 and p27