{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:10Z","timestamp":1785301210836,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072798"],"award-info":[{"award-number":["82072798"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is a highly aggressive brain malignancy driven by glioma stem cells (GSCs). TIGAR (TP53\u2010induced glycolysis and apoptosis regulator) is primarily known as a metabolic regulator that supports cell survival. However, its non\u2010metabolic functions in neuro\u2010oncology remain largely unexplored. This study aims to investigate the structural role of TIGAR in maintaining mitotic spindle integrity and its potential interplay with the ubiquitin\u2010proteasome system in GSCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical relevance of TIGAR expression was evaluated using GEPIA2, TCGA, CGGA, GTEx, and PDX\u2010based analyses. TIGAR function was investigated in human GSC lines (GSC464 and GSC23) using lentiviral shRNA knockdown. Cell cycle progression and spindle morphology were analyzed with flow cytometry and immunofluorescence. Protein\u2013protein interactions and stability were assessed via immunoprecipitation, cycloheximide chase, ubiquitination assays, NAC rescue testing, and Parkin co\u2010depletion rescue assays. In\u00a0vivo effects of TIGAR depletion were evaluated using GSC\u2010derived orthotopic xenografts in SCID mice and an HRas\u2010driven, p53\u2010deficient primary glioblastoma mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TIGAR expression is significantly upregulated in human GBM, correlating with tumor malignancy, stemness features, and poor patient prognosis. Public transcriptomic analysis showed a positive association between TIGAR expression and a GSC\u2010related stemness signature, and double immunofluorescence staining confirmed co\u2010localization of TIGAR with SOX2 or CD133 in two PDX models. TIGAR ablation in GSCs induced G2\/M arrest and severe spindle defects, and these effects were validated in an additional GSC line. Mechanistically, TIGAR localizes to the mitotic spindle and physically interacts with \u03b2II\u2010tubulin, protecting it from Parkin\u2010mediated polyubiquitination and subsequent proteasomal degradation. NAC failed to rescue \u03b2II\u2010tubulin loss after TIGAR knockdown, whereas Parkin co\u2010depletion restored \u03b2II\u2010tubulin levels and partially normalized the G2\/M fraction. In\u00a0vivo, TIGAR knockdown inhibited GSC\u2010driven tumor growth, reduced stemness marker expression, and significantly prolonged animal survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study reveals an essential non\u2010metabolic function of TIGAR in GBM. The TIGAR\u2010Parkin\u2010\u03b2II\u2010tubulin axis serves as a critical mechanism for maintaining mitotic stability and protecting the GSC cytoskeletal network. These findings highlight TIGAR as a structural stabilizer during mitosis and a promising therapeutic target for glioblastoma, independent of p53 mutational status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71033","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:55:27Z","timestamp":1784530527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TIGAR<\/scp>\n                    Maintains Mitotic Spindle Organization and\n                    <scp>\u03b2II<\/scp>\n                    \u2010Tubulin Stability in Glioma Stem Cells"],"prefix":"10.1002","volume":"32","author":[{"given":"Ailin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital of Soochow University  Suzhou 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