{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:37:54Z","timestamp":1792636674081,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fujian Provincial Natural Science Fund","award":["2022J011317"],"award-info":[{"award-number":["2022J011317"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glioblastoma (GBM) is the most aggressive primary brain tumor and has a dismal prognosis. The chaperone protein gp96 is implicated in various cancers but its role and functions in GBM remain poorly defined. This study aimed to investigate the expression, function, and underlying mechanism of gp96 in GBM pathogenesis. gp96 expression was analyzed via the GEPIA2 database. The cell counting kit-8, EdU staining, colony formation and transwell assays were performed to evaluate viability, proliferation, invasion and migration of GBM cell lines. The underlying mechanism was investigated by Kyoto Encyclopedia of Genes and Genomes analysis and Western blot. The results showed that gp96 mRNA and protein levels were upregulated in GBM cells and that gp96 knockdown significantly inhibited viability, proliferation, migration and invasion by the cells. gp96 was found to be enriched in the NF-\u03baB pathway and gp96 knockdown inhibited NF-\u03baB pathway activation in the GBM cells. The NF-\u03baB activator phorbol 12-myristate 13-acetate restored the viability, proliferation, migration, and invasion inhibited by gp96 knockdown. Thus, our findings revealed that gp96 knockdown inhibited the malignant behaviors of GBM by suppressing the NF-\u03baB pathway. This study identifies the gp96\/NF-\u03baB axis as a novel potential therapeutic target for GBM intervention.<\/jats:p>","DOI":"10.1093\/jnen\/nlag111","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:49:08Z","timestamp":1792626548000},"source":"Crossref","is-referenced-by-count":0,"title":["gp96 knockdown inhibits the malignant behaviors of glioblastoma cells by suppressing the NF-\u03baB pathway"],"prefix":"10.1093","author":[{"given":"Chengshi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Emergency, Fuzhou Second Hospital , Fuzhou, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency, Fuzhou Second Hospital , Fuzhou, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengping","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiamen Stemery Biotech Co., Ltd Bld. , Xiamen, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Emergency, Fuzhou Second Hospital , Fuzhou, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency, Fuzhou Second Hospital , Fuzhou, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Ye","sequence":"additional","affiliation":[{"name":"Xiamen Stemery Biotech Co., Ltd Bld. , Xiamen, Fujian,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"2026102121381624900_nlag111-B1","doi-asserted-by":"publisher","first-page":"104764","DOI":"10.1016\/j.critrevonc.2025.104764","article-title":"Glioblastoma: molecular features, emerging molecular targets and novel therapeutic strategies","volume":"212","author":"Politis","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"2026102121381624900_nlag111-B2","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and other primary brain malignancies in adults: a review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"2026102121381624900_nlag111-B3","doi-asserted-by":"publisher","first-page":"n1560","DOI":"10.1136\/bmj.n1560","article-title":"Glioblastoma: clinical presentation, diagnosis, and management","volume":"374","author":"McKinnon","year":"2021","journal-title":"BMJ"},{"key":"2026102121381624900_nlag111-B4","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1101\/gad.351427.123","article-title":"Glioblastoma microenvironment-from biology to therapy","volume":"38","author":"Read","year":"2024","journal-title":"Genes Dev"},{"key":"2026102121381624900_nlag111-B5","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1186\/s12967-024-05301-9","article-title":"The tumour microenvironment, treatment resistance and recurrence in glioblastoma","volume":"22","author":"White","year":"2024","journal-title":"J Transl Med"},{"key":"2026102121381624900_nlag111-B6","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1002\/med.21915","article-title":"The biology and inhibition of glucose-regulated protein 94\/gp96","volume":"42","author":"Pugh","year":"2022","journal-title":"Med Res Rev"},{"key":"2026102121381624900_nlag111-B7","doi-asserted-by":"publisher","first-page":"629846","DOI":"10.3389\/fonc.2021.629846","article-title":"Molecular chaperone GRP94\/GP96 in cancers: oncogenesis and therapeutic target","volume":"11","author":"Duan","year":"2021","journal-title":"Front Oncol"},{"key":"2026102121381624900_nlag111-B8","doi-asserted-by":"publisher","first-page":"mjad27","DOI":"10.1093\/jmcb\/mjad027","article-title":"Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma","volume":"15","author":"Qian","year":"2023","journal-title":"J Mol Cell Biol"},{"key":"2026102121381624900_nlag111-B9","doi-asserted-by":"publisher","first-page":"784777","DOI":"10.3389\/fonc.2021.784777","article-title":"Hypoxia-induced intracellular and extracellular heat shock protein gp96 increases paclitaxel-resistance and facilitates immune evasion in breast cancer","volume":"11","author":"Tian","year":"2021","journal-title":"Front Oncol"},{"key":"2026102121381624900_nlag111-B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cca.2012.12.017","article-title":"HSP72 and gp96 in gastroenterological cancers","volume":"417","author":"Wang","year":"2013","journal-title":"Clin Chim Acta"},{"key":"2026102121381624900_nlag111-B11","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/1748-717X-6-136","article-title":"GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy","volume":"6","author":"Lin","year":"2011","journal-title":"Radiat Oncol"},{"key":"2026102121381624900_nlag111-B12","first-page":"1946","article-title":"Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic clinical significance","volume":"8","author":"Chen","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"2026102121381624900_nlag111-B13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.it.2022.07.004","article-title":"NF-\u03baB: blending metabolism, immunity, and inflammation","volume":"43","author":"Capece","year":"2022","journal-title":"Trends Immunol"},{"key":"2026102121381624900_nlag111-B14","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3390\/cells10020355","article-title":"NF-\u03baB in cancer immunity: friend or foe?","volume":"10","author":"Lalle","year":"2021","journal-title":"Cells"},{"key":"2026102121381624900_nlag111-B15","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in inflammation and cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell Mol Immunol"},{"key":"2026102121381624900_nlag111-B16","doi-asserted-by":"publisher","first-page":"7883","DOI":"10.3390\/ijms26167883","article-title":"The pivotal role of NF-\u03baB in glioblastoma: mechanisms of activation and therapeutic implications","volume":"26","author":"Ramar","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026102121381624900_nlag111-B17","doi-asserted-by":"publisher","first-page":"10337","DOI":"10.3390\/ijms241210337","article-title":"The recent research progress of NF-\u03baB signaling on the proliferation, migration, invasion, immune escape and drug resistance of glioblastoma","volume":"24","author":"Shi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026102121381624900_nlag111-B18","doi-asserted-by":"publisher","first-page":"e180080","DOI":"10.1172\/JCI180080","article-title":"Spatial and functional targeting of intratumoral Tregs reverses CD8+ T cell exhaustion and promotes cancer immunotherapy","volume":"134","author":"Zhou","year":"2024","journal-title":"J Clin Invest"},{"key":"2026102121381624900_nlag111-B19","doi-asserted-by":"crossref","first-page":"7665","DOI":"10.3390\/jcm13247665","article-title":"Predictive and prognostic values of glycoprotein 96, androgen receptors, and extranodal extension in sentinel lymph node-positive breast cancer: an immunohistochemical retrospective study","volume":"13","author":"Klarica Gembi","year":"2024","journal-title":"J Clin Med"},{"key":"2026102121381624900_nlag111-B20","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.molonc.2015.03.004","article-title":"Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR","volume":"9","author":"Hou","year":"2015","journal-title":"Mol Oncol"},{"key":"2026102121381624900_nlag111-B21","doi-asserted-by":"publisher","first-page":"18243","DOI":"10.1074\/jbc.M113.468850","article-title":"\u03b17 helix region of \u03b1I domain is crucial for integrin binding to endoplasmic reticulum chaperone gp96: a potential therapeutic target for cancer metastasis","volume":"288","author":"Hong","year":"2013","journal-title":"J Biol Chem"},{"key":"2026102121381624900_nlag111-B22","doi-asserted-by":"publisher","first-page":"9575867","DOI":"10.1155\/2022\/9575867","article-title":"gp96 expression in gliomas and its association with tumor malignancy and t cell infiltrating level","volume":"2022","author":"Li","year":"2022","journal-title":"J Oncol"},{"key":"2026102121381624900_nlag111-B23","doi-asserted-by":"publisher","first-page":"216709","DOI":"10.1016\/j.canlet.2024.216709","article-title":"S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE\/NF-kB\/VEGF-D pathway","volume":"587","author":"Chen","year":"2024","journal-title":"Cancer Lett"},{"key":"2026102121381624900_nlag111-B24","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1016\/j.humpath.2008.01.020","article-title":"Expression of nuclear factor-kappaB in human astrocytomas: relation to pI kappa Ba, vascular endothelial growth factor, Cox-2, microvascular characteristics, and survival","volume":"39","author":"Korkolopoulou","year":"2008","journal-title":"Hum Pathol"},{"key":"2026102121381624900_nlag111-B25","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/s41418-024-01292-8","article-title":"IFI35 regulates non-canonical NF-\u03baB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages","volume":"31","author":"Li","year":"2024","journal-title":"Cell Death Differ"},{"key":"2026102121381624900_nlag111-B26","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1093\/neuonc\/noab126","article-title":"Spliceosome-regulated RSRP1-dependent NF-\u03baB activation promotes the glioblastoma mesenchymal phenotype","volume":"23","author":"Li","year":"2021","journal-title":"Neuro Oncol"},{"key":"2026102121381624900_nlag111-B27","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1186\/s13046-025-03484-7","article-title":"CSRP2 promotes the glioblastoma mesenchymal phenotype via p130Cas-mediated NF-\u03baB and MAPK pathways","volume":"44","author":"He","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"2026102121381624900_nlag111-B28","doi-asserted-by":"publisher","first-page":"218551","DOI":"10.1016\/j.canlet.2026.218551","article-title":"TRIM21 drives glioblastoma malignancy via ubiquitination-mediated PDGFRA degradation","volume":"653","author":"Gai","year":"2026","journal-title":"Cancer Lett"},{"key":"2026102121381624900_nlag111-B29","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s13046-022-02526-8","article-title":"ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells","volume":"41","author":"Gao","year":"2022","journal-title":"J Exp Clin Cancer Res"}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/advance-article-pdf\/doi\/10.1093\/jnen\/nlag111\/72259654\/nlag111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/advance-article-pdf\/doi\/10.1093\/jnen\/nlag111\/72259654\/nlag111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:38:23Z","timestamp":1792633103000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/advance-article\/doi\/10.1093\/jnen\/nlag111\/8965465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":29,"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlag111","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"article-number":"nlag111"}}