{
  "abstract": "The RAS-MAPK pathway is frequently dysregulated in cancer, leading to malignant transformation. We previously identified a direct interaction between MyD88, a central adaptor of inflammatory signaling, and ERK, the terminal kinase of the RAS-MAPK cascade. Pharmacologic disruption of this ERK-MyD88 complex with a small molecule induces immunogenic cell death and antitumor immunity, suggesting a novel therapeutic strategy. Here, we show that ERK-MyD88 inhibition drives cellular signaling from non-canonical hubs. First, ERK-MyD88 disruption activates an integrated stress response that drives caspase-8-dependent apoptosis through a FADD-independent pathway within p62-ubiquitin aggregates. Second, it promotes assembly of MyD88, IRAK1, and IRAK4 into Myddosomes that produce proinflammatory chemokines independently of TLR or IL-1R activation. These findings demonstrate that perturbation of the ERK-MyD88 complex rewires cellular signaling into cell-autonomous hubs that coordinate caspase activation with chemokine secretion, thereby driving a program of immunogenic cancer cell death.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Nader Hussein"
    },
    {
      "name": "Najwa Skafi"
    },
    {
      "name": "Thuy Ha Pham"
    },
    {
      "name": "Melina Gautier"
    },
    {
      "name": "Francois Virard"
    },
    {
      "name": "Frédérique Fauvet"
    },
    {
      "name": "Léa Magadoux"
    },
    {
      "name": "Christelle Chassot-Lamblot"
    },
    {
      "name": "Anne-Pierre Morel"
    },
    {
      "name": "Christophe Vanbelle"
    },
    {
      "name": "Bassam Badran"
    },
    {
      "name": "Serge Lebecque"
    },
    {
      "name": "Serge Nicolas Manié"
    },
    {
      "name": "Sylvain Lamure"
    },
    {
      "name": "Toufic Renno"
    },
    {
      "name": "Isabelle Coste"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/87e83h6ns0y7g.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09131-z",
  "fulltext_url": null,
  "id": "87e83h6ns0y7g",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://hal.science/hal-05767899v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7171871569",
  "pdf_url": "https://hal.science/hal-05767899/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-30",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/87e83h6ns0y7g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:42Z",
      "native_id": "hal-05767899",
      "source": "hal",
      "url": "https://hal.science/hal-05767899v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Response and Inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "Non-canonical signaling hubs upon inhibition of MyD88-ERK interaction in cancer",
  "title_text": "Non-canonical signaling hubs upon inhibition of MyD88-ERK interaction in cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:42Z",
  "url": "https://research.draconitic.com/paper/87e83h6ns0y7g",
  "venue": "Cell Death and Disease",
  "versions": []
}