{
  "abstract": "Extracellular matrix (ECM) stiffening and metabolic reprogramming are hallmarks of colorectal cancer (CRC) progression; however, the mechanistic link between biomechanical cues and cholesterol metabolism remains poorly defined. Here, we delineate a mechano-metabolic pathway in which matrix stiffness activates the mechanosensitive Ca²⁺ channel Piezo1 to drive structural reorganization of the Golgi apparatus, promoting its close apposition with the endoplasmic reticulum (ER). This organelle remodeling facilitates the proteolytic activation and nuclear translocation of SREBP2, thereby transcriptionally upregulating HMGCR, the rate-limiting enzyme for cholesterol synthesis, and elevating intracellular cholesterol. HMGCR upregulation is functionally essential for stiffness-induced epithelial-mesenchymal transition (EMT) and CRC progression. Mechanistically, HMGCR-mediated cholesterol accumulation promotes phosphorylation of β-catenin at Ser552, which disrupts β-catenin/E-cadherin complexes at adherens junctions, leading to β-catenin nuclear accumulation and EMT execution. Therapeutically, combined pharmacological inhibition of matrix crosslinking and cholesterol synthesis synergistically suppresses tumor growth and invasion while restoring epithelial architecture in vivo. Collectively, these findings reveal that Piezo1-dependent Golgi-ER reorganization triggers SREBP2-driven cholesterol synthesis, ultimately fueling β-catenin-mediated junctional disassembly and metastasis, and highlight the therapeutic promise of co-targeting tumor mechanics and metabolism.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, PR China.",
    "Department of Gastroenterology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, PR China.",
    "Department of Gastroenterology and Hepatology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, PR China.",
    "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, PR China. zhangshutian@ccmu.edu.cn.",
    "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, PR China. xiesian2022@mail.ccmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Min-Yue Yin"
    },
    {
      "affs": [
        2
      ],
      "name": "Xue Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun-Qi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo-Shen Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Chang-Hao Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu-Hang Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Shu-Tian Zhang",
      "orcid": "0000-0003-2356-4397"
    },
    {
      "affs": [
        4
      ],
      "name": "Si-An Xie",
      "orcid": "0000-0003-4365-8411"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7ktzf7y7zpx5b.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09101-5",
  "fulltext_url": "https://europepmc.org/articles/PMC13680387",
  "id": "7ktzf7y7zpx5b",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897141",
  "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": [
    [
      "lcc",
      "QH573-671"
    ],
    [
      "openalex",
      "1306|Cancer, Lipids, and Metabolism"
    ]
  ],
  "openalex": "W7170885029",
  "pdf_url": "https://europepmc.org/articles/PMC13680387?pdf=render",
  "pmcid": "PMC13680387",
  "pmid": "42897141",
  "published": "2026-07-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/7ktzf7y7zpx5b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897141",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897141"
    },
    {
      "first_seen": "2026-10-30T13:46:32Z",
      "native_id": "41179768de91419eaefaa3e2ba9af40f",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41419-026-09101-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Lipids, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.",
  "title_text": "Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:32Z",
  "url": "https://research.draconitic.com/paper/7ktzf7y7zpx5b",
  "venue": "Cell death & disease",
  "versions": []
}