{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:13Z","timestamp":1785405253996,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Hospital Essen","award":["IFORES D\/107"],"award-info":[{"award-number":["IFORES D\/107"]}]},{"award":["IFORES D\/107"],"award-info":[{"award-number":["IFORES D\/107"]}],"id":[{"id":"https:\/\/ror.org\/02na8dn90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glioblastoma (GBM) is an extremely invasive and incurable tumor. We previously reported predominant ALDH1A3 expression at the invasive front of GBM tumors, which was associated with shorter patient survival, and further showed that ALDH1A3 promoted tumor angiogenesis involving plasminogen activator inhibitor-1 (PAI-1). Here, we investigated whether ALDH1A3 drives cell invasion through retinoic acid (RA) and PAI-1 signaling. Analysis of the TCGA-GBM dataset revealed a positive association between ALDH1A3 and PAI-1 (SERPINE1) expression. Overexpression of ALDH1A3 in GBM cells markedly increased PAI-1 mRNA and protein levels, with cellular colocalization of both proteins, accompanied by robust migration and invasion. These effects were reversed by treatment with a pan-RA receptor (RAR) antagonist AGN193109 (AGN), with a specific PAI-1 inhibitor tiplaxtinin (Tip) or by CRISPR\/Cas9-mediated knockout of PAI-1. In a chick chorioallantoic membrane (CAM) model, ALDH1A3-overexpressing cells showed increased invasion, which was reduced by tiplaxtinin (Tip) treatment or PAI-1 knockout. Mechanistically, ChIP-qPCR demonstrated that RA treatment or ALDH1A3 overexpression increased RAR\u03b1 occupancy at the PAI-1 regulatory region, accompanied by increased PAI-1 expression, both of which were diminished by AGN. Collectively, the present study defines an ALDH1A3-RA-PAI-1 signaling axis that contributes to GBM cell motility and invasion.<\/jats:p>","DOI":"10.3390\/cells15121079","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:44:58Z","timestamp":1781484298000},"page":"1079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Signaling Driven by the Stem Cell Marker ALDH1A3 Promotes Glioblastoma Cell Mobility"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhong-Rong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-2690","authenticated-orcid":false,"given":"Rainer","family":"Will","sequence":"additional","affiliation":[{"name":"Core Facility Cellular Tools, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9651-031X","authenticated-orcid":false,"given":"Maike Anna","family":"Busch","sequence":"additional","affiliation":[{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-0644","authenticated-orcid":false,"given":"Nicole","family":"D\u00fcnker","sequence":"additional","affiliation":[{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Dammann","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-1821","authenticated-orcid":false,"given":"Ulrich","family":"Sure","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-024-00516-y","article-title":"Glioma","volume":"10","author":"Weller","year":"2024","journal-title":"Nat. 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