{
  "abstract": "Oncogene activity and mechanical forces individually and collectively drive colorectal cancer, yet the integration of these signals is unknown. We used a patented peristalsis bioreactor to determine how oncogenic KRAS G12C mutations alter the cellular response to colonic peristalsis. Although both healthy intestinal cells (HIEC-6) and KRAS G12C cancer cells (SW837) sensed peristalsis via ERK phosphorylation (1.7-4.7X increase), their mechano-responses diverged significantly. Peristalsis triggered a 9-fold enrichment of LGR5+ cancer stem cells in KRAS G12C cancer cells, an effect absent in healthy HIEC-6 controls. Using Brillouin microscopy, we discovered that KRAS G12C possessed a mechanically primed state exhibiting 9% reduction in Brillouin Full Width at Half Maximum, indicative of lower intracellular viscosity. Peristalsis further decreased intracellular viscosity in KRAS G12C cells by 11.9%, accompanied by pronounced cell elongation, whereas HIEC-6 maintained viscoelastic homeostasis. This KRAS-dependent mechanical agility enabled KRAS G12C cancer cells to leverage, rather than resist peristalsis, resulting in LGR5 enrichment and malignant progression. Pharmacologic KRAS G12C inhibition with sotorasib reduced LGR5+ cells by 50% under peristalsis, reversing the malignant mechanotype. Conversely, introducing KRAS G12C into HIEC-6 disrupted their mechanical homeostasis and significantly increased LGR5, recapitulating the KRAS-dependent mechano-phenotype. Our findings identify a novel KRAS oncogene-mechanics axis, suggesting that targeting the cell’s mechanical state could be a powerful complement to emerging KRAS-directed therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Engineering, Texas A&M University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Astha Lamichhane"
    },
    {
      "affs": [
        0
      ],
      "name": "Vsevolod Cheburkanov"
    },
    {
      "affs": [
        0
      ],
      "name": "Mykyta Kizilov"
    },
    {
      "affs": [
        0
      ],
      "name": "Abhinav Shenoy"
    },
    {
      "affs": [
        0
      ],
      "name": "Audrey G. Head"
    },
    {
      "affs": [
        0
      ],
      "name": "Vladislav Yakovlev"
    },
    {
      "affs": [
        0
      ],
      "name": "Shreya A. Raghavan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/26jgx1bhvnypz.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-68015-6",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-68015-6",
  "id": "26jgx1bhvnypz",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-68015-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1307|Cellular Mechanics and Interactions"
    ]
  ],
  "openalex": "W7160070397",
  "pdf_url": "https://www.nature.com/articles/s41598-026-68015-6_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/26jgx1bhvnypz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:57Z",
      "native_id": "36d06dae9f794842a38693cd564fc7fc",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-68015-6"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Cellular Mechanics and Interactions",
      "subfield": "cell-biology"
    }
  ],
  "title": "Oncogene-mechanics axis: KRAS G12C confers agility enabling malignant mechano-responses to peristalsis in colorectal cancer",
  "title_text": "Oncogene-mechanics axis: KRAS G12C confers agility enabling malignant mechano-responses to peristalsis in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:57Z",
  "url": "https://research.draconitic.com/paper/26jgx1bhvnypz",
  "venue": "Scientific Reports",
  "versions": []
}