{
  "abstract": "Invasive breast and pancreatic cancer cells thrive within a collagen I-rich, poorly perfused extracellular matrix (ECM) network, necessitating robust metabolic adaptation to endure nutrient deficiency, such as glucose starvation. Here we demonstrate that collagen I is critical for the survival and growth of breast and pancreatic cancer cells. Mechanistically, collagen I promotes α2 β1 integrin-dependent S6 phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) and drives the membrane localisation of the LAT1−4F2hc amino acid transporter. This process ensures a sustained intracellular essential amino acid supply, further fuelling mTORC1 signalling and limiting autophagy. This collagen I-driven pathway is essential for cancer cell survival, as inhibiting the activity of α2 β1 integrin or the LAT1-4F2hc transporter significantly reduces cell growth and invasion in both 2D and 3D models. Finally, the clinical relevance of these transporters is underscored by the significant upregulation of LAT1-4F2hc expression in basal-like breast and pancreatic cancer patients, correlating with poor prognosis and drug resistance. Collectively, our findings highlight that targeting the LAT1−4F2hc transporter might represent a highly promising therapeutic strategy to limit cancer cell growth and invasion in highly fibrotic and nutrient-deprived tumours.\n\nHow do invasive breast and pancreatic cancer cells thrive in collagen-rich environments under nutrient stress? This study shows that collagen I promotes mTORC1 activation and drives the localisation of the LAT1-4F2hc amino acid transporter in the membrane, ensuring a sustained intracellular amino acid supply.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biosciences, University of Sheffield, Sheffield, United Kingdom"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mona Nazemi"
    },
    {
      "name": "Bian Yanes"
    },
    {
      "name": "Eric Vancauwenberghe"
    },
    {
      "name": "Ifeoluwa Oyelade"
    },
    {
      "name": "Heather Walker"
    },
    {
      "name": "Elena Rainero"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6nh0prznp2zay.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3003555",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003555",
  "id": "6nh0prznp2zay",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003555",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|PI3K/AKT/mTOR signaling in cancer"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Collagens"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Phosphorylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell adhesion/Integrins"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Autophagic cell death"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Extracellular matrix/Integrins"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNA"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Breast tumors/Breast cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Pancreatic cancer"
    ],
    [
      "plos",
      "/Research and analysis methods/Specimen preparation and treatment/Staining/Cell staining"
    ]
  ],
  "openalex": "W7213549326",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003555&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/6nh0prznp2zay.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pbio.3003555",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003555"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:cancers and neoplasms",
      "subfield": "oncology"
    }
  ],
  "title": "Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation",
  "title_text": "Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/6nh0prznp2zay",
  "venue": "PLOS Biology",
  "versions": []
}