{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:58:54Z","timestamp":1786460334978,"version":"build-2736575974"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA227136"],"award-info":[{"award-number":["R01CA227136"]}]},{"name":"National Cancer Institute","award":["R01CA260443"],"award-info":[{"award-number":["R01CA260443"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R01GM122375"],"award-info":[{"award-number":["R01GM122375"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS079697"],"award-info":[{"award-number":["R01NS079697"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>\n                    To identify therapeutic targets limiting glioblastoma invasion, we applied druggable genome CRISPRi screens and multiomic analysis to patient-derived glioblastoma cells in micro-dissectible biomimetic 3D hydrogels that permitted separation and analysis of core versus invasive fractions. Of 2,550 genes screened, 12 encoded druggable targets whose suppression limited invasion, of which\n                    <jats:italic>AURKB<\/jats:italic>\n                    (encoding aurora kinase B) and\n                    <jats:italic>ACP1<\/jats:italic>\n                    (encoding low molecular weight protein tyrosine phosphatase, LMW-PTP) were validated in neurosphere assays and in vivo. Proximity labeling identified cortactin as a link between LMW-PTP and aurora B, and we observed that cortactin underwent serine phosphorylation by aurora B and tyrosine dephosphorylation by LMW-PTP. Targeting\n                    <jats:italic>ACP1<\/jats:italic>\n                    or\n                    <jats:italic>AURKB<\/jats:italic>\n                    via CRISPRi or inhibitors in culture and in vivo shifted the cortactin phosphorylation balance in glioblastoma, reducing levels of cortactin and the actin-related protein 2\/3 (Arp2\/3) complex that mediates cortactin-induced actin stabilization, thereby reducing actin-cortactin-Arp2\/3 colocalization and subsequent actin polymerization.\n                    <jats:italic>AURKB<\/jats:italic>\n                    or\n                    <jats:italic>ACP1<\/jats:italic>\n                    targeting shifted actin from cytoplasm to the nucleus, reducing mesenchymal gene expression. Biophysical analysis implicated\n                    <jats:italic>AURKB<\/jats:italic>\n                    in glioblastoma cell adhesion and stiffness needed for initial migration and\n                    <jats:italic>ACP1<\/jats:italic>\n                    in mechanical stress resistance required for later migration. These findings revealed a targetable axis balancing kinase and phosphatase activities to regulate actin polymerization during glioblastoma invasion.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>The poor prognosis of glioblastoma, a malignant brain cancer, arises from its invasiveness. We performed a druggable genome screen in glioblastoma cells invading brain-mimetic hydrogels, revealing Aurora B and LMW-PTP as invasion mediators.<\/jats:p>","DOI":"10.1172\/jci.insight.196484","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:44:51Z","timestamp":1786452291000},"source":"Crossref","is-referenced-by-count":0,"title":["Druggable genome CRISPRi screen in hydrogels reveals regulators of cortactin-driven actin remodeling promoting glioblastoma invasion"],"prefix":"10.1172","volume":"11","author":[{"given":"Mufeng","family":"Hu","sequence":"first","affiliation":[{"name":"UCSF Neurosurgery, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Weldy","sequence":"additional","affiliation":[{"name":"UC Berkeley Chemical and Biomolecular Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella 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