{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:15:01Z","timestamp":1771931701910,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Among gastric cancer (GC) cases, stomach adenocarcinoma (STAD) comprises the majority, exceeding 95%. GC develops stealthily and quickly; the majority of cases are detected at advanced or mid-stage, which adversely affects the prognosis. Hence, delving into the molecular mechanisms contributing to GC advancement, and discovering innovative therapeutic targets and latent biomarkers for GC remain at the forefront of research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>QRT-PCR and western blot procedures were followed to make clear the targeting protein for Xklp2 (TPX2) expression in GC and surrounding non-tumor tissues. The impacts of TPX2 overproduction or attenuation on the biological traits of GC cells were examined through CCK-8 assay and transwell assay; meanwhile, vessel formation assays were employed to assess TPX2\u2019s impact on the vascular formation of GC. Furthermore, TCF\/LEF activity was determined using the Top-Flash reporter plasmid; the production of proteins linked to epithelial-mesenchymal transition (EMT) and proteins linked to the Wnt\/\u03b2-catenin pathway was evaluated through western blot. A nude mouse xenograft tumor model was established, and pathological staining was performed to detect tumor proliferation and angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TPX2 level was much higher in GC tissues and cells. When overexpressed, TPX2 contributed to these cells\u2019 viability, motility, infiltration, EMT, and angiogenesis, alongside activation of Wnt\/\u03b2-catenin pathway; whereas, when silenced, TPX2 caused the opposite outcomes. Additionally, TPX2 overproduction enhanced the TCF\/LEF transcriptional activity, while the introduction of a Wnt\/\u03b2-catenin pathway inhibitor partly mitigated the GC advancement enhanced by overproducing TPX2. This phenomenon further confirms that TPX2 exerts carcinogenesis by enabling the Wnt\/\u03b2-catenin pathway. Silencing TPX2 reduced tumor volume and weight in nude mice, inhibited angiogenesis and proliferation, and suppressed EMT\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By activating the Wnt\/\u03b2-catenin pathway, TPX2 promotes GC migration, invasion, and tumor angiogenesis, which collectively drive GC malignant progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1764583","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:22:25Z","timestamp":1770960145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TPX2 promotes gastric cancer progression and angiogenesis via Wnt\/\u03b2-catenin signaling"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Oncology, The First People\u2019 s Hospital of Tongxiang","place":["Jiaxing, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Anorectal Surgery, The First People\u2019s Hospital of Tongxiang","place":["Jiaxing, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12943-020-01185-7","article-title":"Noncoding RNAs in gastric cancer: implications for drug resistance","volume":"19","author":"Wei","year":"2020","journal-title":"Mol Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11912-019-0820-4","article-title":"Updates on management of gastric cancer","volume":"21","author":"Johnston","year":"2019","journal-title":"Curr Oncol Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000506509","article-title":"Gastric cancer: where are we heading","volume":"38","author":"Petryszyn","year":"2020","journal-title":"Dig Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0008","article-title":"Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Ajani","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"B5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13045-023-01451-3","article-title":"Gastric cancer treatment: recent progress and future perspectives","volume":"16","author":"Guan","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1186\/s12957-016-1042-y","article-title":"The patterns and timing of recurrence after curative resection for gastric cancer in China","volume":"14","author":"Liu","year":"2016","journal-title":"World J Surg Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103841","article-title":"Characteristics of gastric cancer around the world","volume":"181","author":"L\u00f3pez","year":"2023","journal-title":"Crit Rev Oncol Hematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.07.045","article-title":"Burden of gastric cancer","volume":"18","author":"Thrift","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201726","article-title":"AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation","volume":"6","author":"Asteriti","year":"2023","journal-title":"Life Sci alliance"},{"key":"B10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s12276-022-00907-9","article-title":"TPX2 prompts mitotic survival via the induction of BCL2L1 through YAP1 protein stabilization in human embryonic stem cells","volume":"55","author":"Kim","year":"2023","journal-title":"Exp Mol Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/eraa513","article-title":"A guide to plant TPX2-like and WAVE-DAMPENED2-like proteins","volume":"72","author":"Smertenko","year":"2021","journal-title":"J Exp Bot"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3368","DOI":"10.1016\/j.celrep.2020.02.041","article-title":"MYC dysregulates mitosis, revealing cancer vulnerabilities","volume":"30","author":"Rohrberg","year":"2020","journal-title":"Cell Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7571066","article-title":"Comprehensive analysis of the oncogenic role of targeting protein for Xklp2 (TPX2) in human Malignancies","volume":"2022","author":"Shao","year":"2022","journal-title":"Dis Markers"},{"key":"B14","doi-asserted-by":"publisher","first-page":"374","DOI":"10.3390\/cells9020374","article-title":"Excess TPX2 interferes with microtubule disassembly and nuclei reformation at mitotic exit","volume":"9","author":"Naso","year":"2020","journal-title":"Cells"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02295-x","article-title":"TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer","volume":"129","author":"Guenther","year":"2023","journal-title":"Br J Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbrc.2021.01.106","article-title":"TPX2 mediates prostate cancer epithelial-mesenchymal transition through CDK1 regulated phosphorylation of ERK\/GSK3\u03b2\/SNAIL pathway","volume":"546","author":"Zhang","year":"2021","journal-title":"Biochem Biophys Res Commun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26340","article-title":"TPX2-p53-GLIPR1 regulatory circuitry in cell proliferation, invasion, and tumor growth of bladder cancer","volume":"119","author":"Yan","year":"2018","journal-title":"J Cell Biochem"},{"key":"B18","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3892\/or.2023.8553","article-title":"Bioinformatics and experimental validation of an AURKA\/TPX2 axis as a potential target in esophageal squamous cell carcinoma","volume":"49","author":"Du","year":"2023","journal-title":"Oncol Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12957-016-1095-y","article-title":"TPX2 expression is associated with poor survival in gastric cancer","volume":"15","author":"Tomii","year":"2017","journal-title":"World J Surg Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal transduction targeted Ther"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1587950","article-title":"Interplay between tumor cells and immune cells of the colorectal cancer tumor microenvironment: Wnt\/\u03b2-catenin pathway","volume":"16","author":"Janeeh","year":"2025","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112175","article-title":"Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt\/\u03b2-catenin pathway","volume":"134","author":"Ye","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01747-0","article-title":"CCT5 induces epithelial-mesenchymal transition to promote gastric cancer lymph node metastasis by activating the Wnt\/\u03b2-catenin signalling pathway","volume":"126","author":"Li","year":"2022","journal-title":"Br J Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2478\/raon-2024-0007","article-title":"RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt\/\u03b2-catenin pathway","volume":"58","author":"Li","year":"2024","journal-title":"Radiol Oncol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.2147\/ott.S401454","article-title":"Transmission of exosomal TPX2 promotes metastasis and resistance of NSCLC cells to docetaxel","volume":"16","author":"Hu","year":"2023","journal-title":"Onco Targets Ther"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.62382\/jcbt.v1i1.1","article-title":"The influence of miR-3149 on the Malignancy progression of gastric cancer by negatively regulating CEACAM5","volume":"1","author":"Zhao","year":"2024","journal-title":"J Cancer Biomoleculars Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.62382\/jcbt.v2i1.51","article-title":"Ginsenoside Rh4 suppresses Notch3 and PI3K\/Akt pathway to inhibit growth and metastasis of gastric cancer cells","volume":"2","author":"Beeraka","year":"2025","journal-title":"J Cancer Biomoleculars Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c01782","article-title":"MGST1 expression is associated with poor prognosis, enhancing the Wnt\/\u03b2-catenin pathway via regulating AKT and inhibiting ferroptosis in gastric cancer","volume":"8","author":"Li","year":"2023","journal-title":"ACS omega"},{"key":"B29","doi-asserted-by":"publisher","first-page":"jcs258356","DOI":"10.1242\/jcs.258356","article-title":"Importin \u03b1 phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation","volume":"134","author":"Guo","year":"2021","journal-title":"J Cell Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-023-10514-4","article-title":"TPX2 amplification-driven aberrant mitosis in culture adapted human embryonic stem cells with gain of 20q11.21","volume":"19","author":"Jeong","year":"2023","journal-title":"Stem Cell Rev Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s12964-023-01290-2","article-title":"Therapeutic targeting of the TPX2\/TTK network in colorectal cancer","volume":"21","author":"Shaath","year":"2023","journal-title":"Cell communication signaling: CCS"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2015.11.007","article-title":"TPX2 promotes migration and invasion of human breast cancer cells","volume":"8","author":"Yang","year":"2015","journal-title":"Asian Pac J Trop Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2016.1195046","article-title":"Overexpressed targeting protein for Xklp2 (TPX2) serves as a promising prognostic marker and therapeutic target for gastric cancer","volume":"17","author":"Liang","year":"2016","journal-title":"Cancer Biol Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12935-016-0357-7","article-title":"Expression of microtubule-associated protein TPX2 in human gastric carcinoma and its prognostic significance","volume":"16","author":"Shao","year":"2016","journal-title":"Cancer Cell Int"},{"key":"B35","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1186\/s13046-020-01709-5","article-title":"The role of microenvironment in tumor angiogenesis","volume":"39","author":"Jiang","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03351-7","article-title":"Tumor angiogenesis: causes, consequences, challenges and opportunities","volume":"77","author":"Lugano","year":"2020","journal-title":"Cell Mol Life Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2174\/1389200221666201019143252","article-title":"Tumor angiogenesis and VEGFR-2: mechanism, pathways and current biological therapeutic interventions","volume":"22","author":"Shah","year":"2021","journal-title":"Curr Drug Metab"},{"key":"B38","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/jcm9010084","article-title":"Tumor angiogenesis and anti-angiogenic strategies for cancer treatment","volume":"9","author":"Teleanu","year":"2019","journal-title":"J Clin Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41392-023-01460-1","article-title":"Angiogenic signaling pathways and anti-angiogenic therapy for cancer","volume":"8","author":"Liu","year":"2023","journal-title":"Signal transduction targeted Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.09.129","article-title":"A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions","volume":"221","author":"Vimalraj","year":"2022","journal-title":"Int J Biol Macromol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00696","article-title":"Dual effects of Chinese herbal medicines on angiogenesis in cancer and ischemic stroke treatments: role of HIF-1 network","volume":"10","author":"Hong","year":"2019","journal-title":"Front Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.04.026","article-title":"Salinomycin inhibits breast cancer progression via targeting HIF-1\u03b1\/VEGF mediated tumor angiogenesis in vitro and in vivo","volume":"164","author":"Dewangan","year":"2019","journal-title":"Biochem Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12739","article-title":"Enhanced anti-angiogenic activity of novel melatonin-like agents","volume":"71","author":"Hwang","year":"2021","journal-title":"J Pineal Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1007\/s12672-024-01502-2","article-title":"HOXC12 promotes the invasion and migration of gastric cancer cells by upregulating SALL4 and activating Wnt\/\u03b2-catenin signaling pathway","volume":"15","author":"Zhang","year":"2024","journal-title":"Discover Oncol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41392-022-01190-w","article-title":"Signaling pathways and therapeutic interventions in gastric cancer","volume":"7","author":"Lei","year":"2022","journal-title":"Signal transduction targeted Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102831","article-title":"SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt\/\u03b2-catenin signaling pathway","volume":"12","author":"Tian","year":"2020","journal-title":"Aging (Albany N Y)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28119","article-title":"Effect and mechanism of lentivirus-mediated silencing of TPX2 gene on proliferation and apoptosis of human hepatoma cells","volume":"120","author":"Ding","year":"2019","journal-title":"J Cell Biochem"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1764583\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:28:06Z","timestamp":1771928886000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1764583\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":47,"alternative-id":["10.3389\/fonc.2026.1764583"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1764583","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"article-number":"1764583"}}