{
  "abstract": "Validated biomarkers for identifying patients with early-stage melanomas at high risk of metastasis are limited. We have previously shown that loss of Activating Molecule in Beclin-1-Regulated Autophagy (AMBRA1) and loricrin in the epidermal microenvironment is associated with tumour recurrence. Here we show that endothelial AMBRA1 deficiency contributes to vascular dysfunction and melanoma progression. Melanoma-conditioned media or exposure to TGF{beta}1-3 ligands induced post-transcriptional loss of AMBRA1 in endothelial cells. Transcriptomic profiling in both in vitro and human melanoma single-cell RNA sequencing datasets showed activation of cell-cycle and metabolic programmes alongside suppression of endothelial junction, adhesion and immune-supportive pathways in AMBRA1-deficient endothelial cells. Functionally, AMBRA1 loss increased endothelial cell proliferation, accelerated early tubulogenesis, impaired three-dimensional spheroid adhesion, stabilised endothelial-to-mesenchymal transition-associated transcription factors Slug and Snail, and reduced Claudin-5, VE-cadherin and N-cadherin, indicative of endothelial plasticity and dysfunction. Furthermore, loss of AMBRA1 in a subset of intratumoural and peritumoural blood and lymphatic vessels correlated significantly with metastatic progression in a cohort of 121 non-ulcerated primary AJCC stage I/II melanomas classified as AMBLor at-risk. Collectively, these findings position endothelial AMBRA1 as a regulator of vascular plasticity, dysfunction, and immune-supportive endothelial function in early-stage melanomas, and a marker of a permissive microenvironment associated with metastasis.",
  "abstract_shown": true,
  "affiliations": [
    "John Dawson Drug Discovery and Development Research Institute, University of Sunderland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "L. Walker"
    },
    {
      "name": "R. Stout"
    },
    {
      "name": "M. Di Rienzo"
    },
    {
      "name": "K. Best"
    },
    {
      "name": "S. Bisegna"
    },
    {
      "name": "L. Occhigrossi"
    },
    {
      "name": "I. Cosgarea"
    },
    {
      "name": "P. Sloan"
    },
    {
      "name": "G. Richardson"
    },
    {
      "name": "R. Strippoli"
    },
    {
      "name": "M. Piacentini"
    },
    {
      "name": "G. M. Fimia"
    },
    {
      "name": "P. E. Lovat"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Armstrong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ek0esbjzk0dwh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.29.755318",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755318v1.full",
  "id": "ek0esbjzk0dwh",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755318v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7214947202",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755318v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ek0esbjzk0dwh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:24Z",
      "native_id": "10.64898/2026.09.29.755318",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755318v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Endothelial AMBRA1 loss contributes to vascular dysregulation facilitating metastatic progression in early-stage melanoma",
  "title_text": "Endothelial AMBRA1 loss contributes to vascular dysregulation facilitating metastatic progression in early-stage melanoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:24Z",
  "url": "https://research.draconitic.com/paper/ek0esbjzk0dwh",
  "venue": "bioRxiv",
  "versions": []
}