{
  "abstract": "Palmitate-associated lipotoxic stress activates the endoplasmic-reticulum stress sensor protein IRE1, but how IRE1 signaling influences genotoxic-stress responses in triple-negative breast cancer remains unclear. Here, we investigated IRE1 and XBP1 signaling in MDA-MB-231 cells exposed to palmitate and etoposide. Under combined lipotoxic and genotoxic stress, XBP1 depletion increased DNA-damage accumulation in IRE1 wild-type cells but not in IRE1-deficient cells, whereas IRE1 re-expression reduced DNA damage. Pharmacologic IRE1 RNase inhibition also increased etoposide-associated DNA damage, supporting a protective role for IRE1 RNase-dependent signaling. IRE1 status and XBP1 manipulation differentially affected H2A.X and {gamma}H2A.X abundance, indicating context-dependent regulation of chromatin-associated DNA-damage signaling. At the RNA level, H2A.X was enriched in IRE1 immunoprecipitates, and the H2A.X-linked DNA-damage-response transcripts HUWE1 and BRCA2 also associated with IRE1 under combined stress. These findings link palmitate-activated IRE1-XBP1 signaling to genome-protective responses during genotoxic stress and identify a network of IRE1-associated DNA-damage-response transcripts in triple-negative breast cancer cells. Direct IRE1-mediated cleavage of these transcripts remains to be established.",
  "abstract_shown": true,
  "affiliations": [
    "Michigan State University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "K. Y. Chen"
    },
    {
      "name": "E. Gouin"
    },
    {
      "name": "A. Erickson"
    },
    {
      "name": "Y. Goyal"
    },
    {
      "name": "S. Zaloudek"
    },
    {
      "name": "S. Foster"
    },
    {
      "name": "C. Sandum"
    },
    {
      "name": "S. P. Walton"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Chan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9pbc5n9ch5spk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754433",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754433v1.full",
  "id": "9pbc5n9ch5spk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754433v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7214656566",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754433v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9pbc5n9ch5spk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:50Z",
      "native_id": "10.64898/2026.09.25.754433",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754433v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Palmitate-activated IRE1-XBP1 signaling limits DNA damage and is associated with H2A.X-linked DNA damage response transcripts in triple-negative breast cancer cells",
  "title_text": "Palmitate-activated IRE1-XBP1 signaling limits DNA damage and is associated with H2A.X-linked DNA damage response transcripts in triple-negative breast cancer cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:50Z",
  "url": "https://research.draconitic.com/paper/9pbc5n9ch5spk",
  "venue": "bioRxiv",
  "versions": []
}