{
  "abstract": "Background: MYH9 is upregulated in various malignancies, but its role in breast cancer chemoresistance remains unclear. We investigated whether MYH9 regulates doxorubicin (ADR) resistance via GRP78 stabilization and PERK pathway modulation.\n\nMethods: MYH9 expression was analyzed in breast cancer tissues and cell lines by immunohistochemistry and western blot. ADR-resistant MCF-7 and MDA-MB-231 cell lines were established. MYH9 knockdown/overexpression and GRP78 overexpression were achieved by lentiviral transduction. Protein interactions, degradation assays, PERK signaling, apoptosis, and in vivo drug responses were evaluated.\n\nResults: MYH9 was significantly upregulated in breast cancer tissues, particularly in triple-negative breast cancer (95.2%), and further elevated in ADR-resistant cells. MYH9 overexpression enhanced ADR tolerance, while knockdown sensitized resistant cells in vitro and in vivo . Mechanistically, MYH9 directly bound GRP78 (but not CALR or GRP94), inhibiting ubiquitin-mediated proteasomal degradation. MYH9 depletion reduced GRP78 levels and activated the PERK pathway (p-eIF2α, ATF4, CHOP), promoting apoptosis via Bax/Bad upregulation and Bcl-2 downregulation. ERS induction with thapsigargin enhanced ADR sensitivity, whereas 4-PBA attenuated it. GRP78 overexpression rescued ADR resistance, confirming GRP78 dependency.\n\nConclusion: MYH9 confers ADR resistance in breast cancer by stabilizing GRP78 and suppressing PERK-driven apoptosis, identifying the MYH9/GRP78 axis as a potential therapeutic target for overcoming chemoresistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Breast Surgery, Ningbo No. 2 Hospital, Wenzhou Medical University , , ,",
    "Department if Dermatology, Traditional Chinese Medicine Hospital of Ninghai County , , ,",
    "Health Science Center, Ningbo University , , ,",
    "School of Medicine, ShaoXing University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jing Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Tianzi You"
    },
    {
      "affs": [
        2
      ],
      "name": "Ziyi Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Binlei Sheng"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhanqi Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Xujun Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bjvjgf41cbwzv.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1923603",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672191/?tool=EBI",
  "id": "bjvjgf41cbwzv",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672191",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7215100395",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672191/pdf/?tool=EBI",
  "pmcid": "PMC13672191",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bjvjgf41cbwzv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:25Z",
      "native_id": "PMC:PMC13672191",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13672191"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1923603",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1923603/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Endoplasmic Reticulum Stress and Disease",
      "subfield": "cell-biology"
    }
  ],
  "title": "MYH9 confers doxorubicin resistance by stabilizing GRP78 and suppressing the PERK signaling-driven apoptotic pathway in breast cancer",
  "title_text": "MYH9 confers doxorubicin resistance by stabilizing GRP78 and suppressing the PERK signaling-driven apoptotic pathway in breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/bjvjgf41cbwzv",
  "venue": "Frontiers in oncology",
  "versions": []
}