{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Franovic A"],"funding":["NCI NIH HHS","Canadian Institutes of Health Research"],"pagination":["4466-73"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4631634"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["75(21)"],"pubmed_abstract":["Integrin ?v?3 has been implicated as a driver of aggressive and metastatic disease, and is upregulated during glioblastoma progression. Here, we demonstrate that integrin ?v?3 allows glioblastoma cells to counteract senescence through a novel tissue-specific effector mechanism involving recruitment and activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting either ?v?3 or PAK4 led to emergence of a p21-dependent, p53-independent cell senescence phenotype. Notably, glioblastoma cells did not exhibit a similar requirement for either other integrins or additional PAK family members. Moreover, ?v?3/PAK4 dependence was not found to be critical in epithelial cancers. Taken together, our findings established that glioblastomas are selectively addicted to this pathway as a strategy to evade oncogene-induced senescence, with implications that inhibiting the ?v?3-PAK4 signaling axis may offer novel therapeutic opportunities to target this aggressive cancer."],"journal":["Cancer research"],"pubmed_title":["Glioblastomas require integrin ?v?3/PAK4 signaling to escape senescence."],"pmcid":["PMC4631634"],"funding_grant_id":["R01 CA045726","R01 CA45726","R01 CA168692"],"pubmed_authors":["Elliott KC","Cheresh DA","Weis SM","Camargo MF","Franovic A","Seguin L"],"additional_accession":[]},"is_claimable":false,"name":"Glioblastomas require integrin ?v?3/PAK4 signaling to escape senescence.","description":"Integrin ?v?3 has been implicated as a driver of aggressive and metastatic disease, and is upregulated during glioblastoma progression. Here, we demonstrate that integrin ?v?3 allows glioblastoma cells to counteract senescence through a novel tissue-specific effector mechanism involving recruitment and activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting either ?v?3 or PAK4 led to emergence of a p21-dependent, p53-independent cell senescence phenotype. Notably, glioblastoma cells did not exhibit a similar requirement for either other integrins or additional PAK family members. Moreover, ?v?3/PAK4 dependence was not found to be critical in epithelial cancers. Taken together, our findings established that glioblastomas are selectively addicted to this pathway as a strategy to evade oncogene-induced senescence, with implications that inhibiting the ?v?3-PAK4 signaling axis may offer novel therapeutic opportunities to target this aggressive cancer.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2020-11-19T15:30:20Z","creation":"2019-03-27T02:01:16Z"},"accession":"S-EPMC4631634","cross_references":{"pubmed":["26297735"],"doi":["10.1158/0008-5472.CAN-15-0988","10.1158/0008-5472.can-15-0988"]}}