{
  "abstract": "Background: Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy with limited therapeutic options for advanced disease. Timosaponin AIII (TSAIII), a natural steroidal saponin, exhibits antitumor activity; however, its effects on NPC progression and the molecular mechanisms remain unclear. Method: Cell viability, proliferation, apoptosis, migration, and invasion were evaluated using cell growth, colony formation, Annexin V/PI, and Transwell assays. Human chemokine array and The Cancer Genome Atlas (TCGA) analyses identified midkine (MDK) as a potential molecular target of TSAIII and its clinical relevance in NPC. Western blotting, qRT-PCR, immunofluorescence, and chromatin immunoprecipitation (ChIP) assays were used to investigate the underlying signaling mechanisms. Antimetastatic activity was further evaluated in C.B17-SCID mice. Results: TSAIII suppressed NPC cell migration and invasion with minimal cytotoxicity, accompanied by reduced the expression of p-AKT (Ser473), estrogen receptor β(ERβ) nuclear localization, and MDK expression. Wortmannin enhanced these effects, while TSAIII attenuated latent membrane protein 1 (LMP1)-induced signaling. In vivo, TSAIII significantly reduced lung metastasis without apparent toxicity. Conclusions: TSAIII suppresses NPC metastasis by targeting the LMP1/p-AKT/ERβ/MDK signaling axis, supporting its potential as an antimetastatic therapeutic candidate for NPC.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan",
    "Department of Medicine Research, Buddhist Dalin Tzu Chi Hospital, Chiayi 62247, Taiwan",
    "Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan",
    "School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan",
    "Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chu-Che Lee",
      "orcid": "0009-0007-6343-0488"
    },
    {
      "affs": [
        2
      ],
      "name": "Yong-Syuan Chen",
      "orcid": "0000-0001-5123-4729"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Shun-Fa Yang",
      "orcid": "0000-0002-0365-7927"
    },
    {
      "affs": [
        0
      ],
      "name": "Chu-Liang Lin"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yi-Hsien Hsieh",
      "orcid": "0000-0003-4942-1888"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Chun-Yi Chuang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fpsbrcp18bbnc.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15211989",
  "fulltext_url": null,
  "id": "fpsbrcp18bbnc",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/21/1989",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fpsbrcp18bbnc.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:24:04Z",
      "native_id": "10.3390/cells15211989",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/21/1989"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2073-4409",
      "subfield": "cell-biology"
    }
  ],
  "title": "Disruption of p-AKT/ERβ-Mediated Midkine Signaling Promotes the Antimetastatic Effects of Timosaponin AIII in Nasopharyngeal Carcinoma Cells",
  "title_text": "Disruption of p-AKT/ERβ-Mediated Midkine Signaling Promotes the Antimetastatic Effects of Timosaponin AIII in Nasopharyngeal Carcinoma Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:24:56Z",
  "url": "https://research.draconitic.com/paper/fpsbrcp18bbnc",
  "venue": "Cells",
  "versions": []
}