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However, the molecular basis connecting invasion, metabolic detectability, and treatment resistance remains elusive. Here, we identify Coronin-1A (Coro1A), a cytoplasmic actin-associated regulator, as a multidirectional modulator of cancer stemness in GBM. Across six patient-derived GBM lines, Coro1A mRNA expression strongly correlated with both cell motility and the proportion of 5-aminolevulinic acid (5-ALA)\u2013negative cells, and high Coro1A levels predicted significantly poorer prognosis in recurrent GBM cases. To assess its function, Coro1A-knockdown clones were generated from a recurrent GBM\u2013derived culture (PDM123). Silencing Coro1A significantly reduced migration and modestly decreased proliferation, with the extent of motility reduction correlating with residual Coro1A expression. Importantly, knockdown enhanced intracellular accumulation of protoporphyrin IX (PpIX) under 5-ALA treatment, even in highly motile cells, indicating that Coro1A simultaneously governs invasiveness and intraoperative fluorescence detectability. Furthermore, Coro1A depletion increased sensitivity to temozolomide (TMZ) and X-ray irradiation, revealing its critical contribution to therapy resistance. Collectively, these findings establish Coro1A as a central cytoskeletal regulator that unifies invasion, diagnostic escape, and therapeutic resilience\u2014highlighting its potential as a curative target capable of dismantling the multifaceted resistance of GBM.<\/jats:p>","DOI":"10.1038\/s41598-026-55120-9","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:54:28Z","timestamp":1779969268000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The cytoskeletal regulator Coronin-1A plays a multidirectional role in glioblastoma stemness"],"prefix":"10.1038","volume":"16","author":[{"given":"TingTing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiyo","family":"Shibahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuichiro","family":"Hide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kumabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Ichiro","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Taga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouichi","family":"Tabu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"issue":"12 Suppl 2","key":"55120_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noaa200","volume":"22","author":"QT Ostrom","year":"2020","unstructured":"Ostrom, Q. 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