{
  "abstract": "Background: Ferroptosis has emerged as a potential avenue for cancer therapy; however, the molecular mechanisms regulating ferroptosis resistance in osteosarcoma (OS) remain incompletely understood. This study aimed to investigate the role of targeting protein for Xklp2 ( TPX2 ) in OS progression and ferroptosis, focusing on the aurora kinase A ( AURKA ) / nuclear factor erythroid 2-related factor 2 ( NRF2 ) signaling axis. Methods: OS-related genes were screened from GSE16088 and GSE42352, followed by functional enrichment, protein-protein interaction (PPI), and receiver operating characteristic (ROC) analyses. TPX2 expression and function in OS cells were evaluated via quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, cell counting kit-8 (CCK-8), colony formation, and flow cytometry. Ferroptosis was evaluated in U2OS cells by cellular sensitivity to erastin/RSL3, reactive oxygen species (ROS) accumulation, Fe 2+ , malondialdehyde (MDA) levels, glutathione (GSH) redox status, and solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) expression. TPX2 and AURKA interaction in U2OS cells was probed using rescue and co-immunoprecipitation (Co-IP) experiments. The stability and ubiquitination level of NRF2 protein were detected using a cycloheximide (CHX) tracing assay and ubiquitination assay. Potential AURKA phosphorylation sites on NRF2 were further assessed using sequence-based kinase scoring. Results: TPX2 was abundantly expressed in OS and facilitated cell proliferation, clonogenicity, and G2-phase advancement. In U2OS cells, TPX2 depletion increased sensitivity to erastin and RSL3, ROS, Fe 2+ , and MDA levels and decreased GSH/GSSG, SLC7A11, and GPX4, which were partially reversed by ferrostatin-1. TPX2 interacted with AURKA, and rescue studies supported AURKA involvement in TPX2-dependent ferroptosis regulation. AURKA sustained NRF2 protein stability by reducing its ubiquitination and degradation. However, no NRF2 site reached the predefined AURKA scoring threshold. TPX2 overexpression had anti-ferroptotic effects, which were suppressed by NRF2 silencing. Conclusion: TPX2 contributes to OS cell proliferation and ferroptosis resistance in U2OS cells through an AURKA/NRF2 -associated mechanism. Direct NRF2 phosphorylation by AURKA remains unproven, and the ferroptosis mechanism requires validation in additional OS models.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedic Surgery, Zhejiang Hospital, Hangzhou 310030, China",
    "Corresponding author."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huashun Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lan Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Biao Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Jingtao Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ahnk799whfypk.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbo.2026.100807",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2212137426000692",
  "id": "ahnk799whfypk",
  "issns": [
    "2212-1374"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbo.2026.100807",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "lcc",
      "RC925-935"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7221307627",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2212137426000692/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ahnk799whfypk.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T14:22:26Z",
      "native_id": "00d819f4fac848ff8ebb1cd58a519cf2",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.jbo.2026.100807"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC254-282",
      "subfield": "oncology"
    }
  ],
  "title": "TPX2 promotes osteosarcoma progression by conferring ferroptosis resistance through the AURKA/NRF2 signaling axis",
  "title_text": "TPX2 promotes osteosarcoma progression by conferring ferroptosis resistance through the AURKA/NRF2 signaling axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:22:26Z",
  "url": "https://research.draconitic.com/paper/ahnk799whfypk",
  "venue": "Journal of Bone Oncology",
  "versions": []
}