{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:47:45Z","timestamp":1792097265194,"version":"4.4.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK Research and Innovation Future Leaders","award":["MR\/T04358X\/1"],"award-info":[{"award-number":["MR\/T04358X\/1"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C16583\/A28803"],"award-info":[{"award-number":["C16583\/A28803"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A31287"],"award-info":[{"award-number":["A31287"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C596\/A17196"],"award-info":[{"award-number":["C596\/A17196"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CRUK Institute","award":["A23983"],"award-info":[{"award-number":["A23983"]}]},{"name":"CRUK Fellowship","award":["C52808\/A23920"],"award-info":[{"award-number":["C52808\/A23920"]}]},{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/T001895\/1"],"award-info":[{"award-number":["NC\/T001895\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002203","name":"Brain Tumour Charity","doi-asserted-by":"publisher","award":["ET_2019\/1_10403"],"award-info":[{"award-number":["ET_2019\/1_10403"]}],"id":[{"id":"10.13039\/501100002203","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist that counter glioblastoma invasion. Here, we report that inhibition of ataxia telangiectasia and Rad 3 related kinase (ATR) reduces invasion of glioblastoma cells through dysregulation of cytoskeletal networks and subsequent integrin trafficking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Glioblastoma motility and invasion were assessed in vitro and in vivo in response to ATR inhibition (ATRi) and ATR overexpression using time-lapse microscopy, two orthotopic glioblastoma models, and intravital imaging. Disruption to cytoskeleton networks and endocytic processing were investigated via high-throughput, super-resolution and intravital imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High ATR expression was associated with significantly poorer survival in clinical datasets while histological, protein expression, and spatial transcriptomics using glioblastoma tumor specimens revealed higher ATR expression at infiltrative margins. Pharmacological inhibition with two different compounds and RNAi targeting of ATR opposed the invasion of glioblastoma, whereas overexpression of ATR drove migration. Subsequent investigation revealed that cytoskeletal dysregulation reduced macropinocytotic internalization of integrins at growth-cone-like structures, resulting in a tumor microtube retraction defect. The biological relevance and translational potential of these findings were confirmed using two orthotopic in vivo models of glioblastoma and intravital imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrate a novel role for ATR in determining invasion in glioblastoma cells and propose that pharmacological targeting of ATR could have far-reaching clinical benefits beyond radiosensitization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noad210","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T09:26:22Z","timestamp":1699003582000},"page":"625-639","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis"],"prefix":"10.1093","volume":"26","author":[{"given":"Sarah J","family":"Derby","sequence":"first","affiliation":[{"name":"Wolfson Wohl Translational Cancer Research Centre, School of Cancer Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Dutton","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Translational Cancer Research Centre, School of Cancer Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E","family":"Strathdee","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Translational Cancer Research Centre, School of Cancer Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Translational Cancer Research Centre, School of Cancer Sciences, University 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Scotland Institute , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Translational Cancer Research Centre, School of Cancer Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thomason","sequence":"additional","affiliation":[{"name":"CRUK Scotland Institute , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan","family":"McGhee","sequence":"additional","affiliation":[{"name":"CRUK Scotland Institute , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor L","family":"McGarrity-Cottrell","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield Medical School , Sheffield , 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