{
  "abstract": "E-cadherin suppresses invasion and promotes metastasis in invasive ductal breast cancer, through suppression of reactive oxygen species (ROS). We sought to determine the cellular source of apoptosis-inducing ROS and to identify the domains of E-cadherin that are essential for cancer cell survival. Inhibition of mitochondria-derived ROS was sufficient to rescue cell death following E-cadherin deletion, in both 3D colony formation and in vivo metastasis assays. We next generated Cdh1 constructs by mutating amino acids or deleting domains, then tested their ability to rescue colony formation in E-cadherin-deleted cells. Surprisingly, E-cadherin constructs in which the extracellular domains were deleted, adhesion was compromised, or catenin interactions were blocked could rescue elevated mitochondrial ROS and 3D colony formation. Conversely, a construct lacking the cytoplasmic domain was unable to rescue ROS or cell death. Our findings reveal that E-cadherin's ability to regulate mitochondrial ROS, cancer cell survival, and metastatic outgrowth is separable from its role in intercellular adhesion.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.",
    "Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.",
    "Giovanis Institute for Translational Cell Biology, The Johns Hopkins University School of Medicine , Baltimore, MD, USA.",
    "Department of Physiology, Pharmacology and Therapeutics, Mitochondrial Phospholipid Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.",
    "Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut School of Medicine, Farmington, CT, USA.",
    "Organ Pathobiology and Therapeutics Institute, The University of Pittsburgh , Pittsburgh, PA, USA.",
    "Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ryan L Huizar",
      "orcid": "0000-0003-4695-9674"
    },
    {
      "affs": [
        0
      ],
      "name": "James V McCann",
      "orcid": "0009-0006-3868-4438"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Malak Amer",
      "orcid": "0000-0003-0590-3156"
    },
    {
      "affs": [
        0
      ],
      "name": "Beza Woldemeskel",
      "orcid": "0000-0003-4988-4989"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Murata",
      "orcid": "0000-0003-3829-6620"
    },
    {
      "affs": [
        3
      ],
      "name": "Nanami Senoo",
      "orcid": "0000-0001-5260-3848"
    },
    {
      "affs": [
        4
      ],
      "name": "Abhijit Deb Roy",
      "orcid": "0000-0003-1640-2402"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Benjamin C Orsburn",
      "orcid": "0000-0002-0774-3750"
    },
    {
      "affs": [
        3
      ],
      "name": "Steven M Claypool",
      "orcid": "0000-0001-5316-1623"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiromi Sesaki",
      "orcid": "0000-0002-6877-3929"
    },
    {
      "affs": [
        0
      ],
      "name": "Miho Iijima",
      "orcid": "0000-0002-3073-9135"
    },
    {
      "affs": [
        5
      ],
      "name": "Namandjé N Bumpus",
      "orcid": "0000-0002-6096-3824"
    },
    {
      "affs": [
        0
      ],
      "name": "Takanari Inoue",
      "orcid": "0000-0002-7957-7624"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Andrew J Ewald",
      "orcid": "0000-0002-1964-0740"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/964cp1w224syc.bib",
  "cited_by": 0,
  "doi": "10.1083/jcb.202507222",
  "fulltext_url": "https://europepmc.org/articles/PMC13689684",
  "id": "964cp1w224syc",
  "issns": [
    "0021-9525",
    "1540-8140"
  ],
  "landing_url": "https://europepmc.org/article/MED/42911134",
  "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",
      "2723|Cell Adhesion Molecules Research"
    ]
  ],
  "openalex": "W7204811399",
  "pdf_url": "https://europepmc.org/articles/PMC13689684?pdf=render",
  "pmcid": "PMC13689684",
  "pmid": "42911134",
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/964cp1w224syc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42911134",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42911134"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2723|Cell Adhesion Molecules Research",
      "subfield": "immunology"
    }
  ],
  "title": "Nonadhesive functions of E-cadherin promote cancer cell survival and metastasis.",
  "title_text": "Nonadhesive functions of E-cadherin promote cancer cell survival and metastasis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/964cp1w224syc",
  "venue": "The Journal of cell biology",
  "versions": []
}