Evidence map›Paper›PMID 39485528›Full record

ArticleMolecular cancer research : MCR2025

Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells.

Abigail J Clevenger, Claudia A Collier, John Paul M Gorley, Sarah Colijn, Maygan K McFarlin, Spencer C Solberg, Scott Kopetz, Amber N Stratman, Shreya A Raghavan

Abstract read
In one paragraph

Article in Molecular cancer research : MCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
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  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Abigail J ClevengerDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0000-0002-1242-8130
Claudia A CollierDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0000-0002-3440-2863
John Paul M GorleyDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0009-0004-9375-0229
Sarah ColijnDepartment of Cell Biology and Physiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.ORCID 0000-0003-3419-9970
Maygan K McFarlinDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0009-0008-6296-1508
Spencer C SolbergDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0009-0009-8902-6672
Scott KopetzDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9647-3416
Amber N StratmanDepartment of Cell Biology and Physiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.ORCID 0000-0002-8111-4186
Shreya A RaghavanDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas.ORCID 0000-0002-4631-7762

Funding

Mechanosensitive mechanisms regulating cellular coordination during tissue morphogenesis and patterningR35GM137976 · NIGMS · WASHINGTON UNIVERSITY · PI STRATMAN, AMBER NICOLE · 2020 to 2024
$2.4M
3D Engineered Model of Microscopic Colorectal Cancer Liver Metastasis for Adjuvant Chemotherapy ScreensR37CA269224 · NCI · TEXAS ENGINEERING EXPERIMENT STATION · PI Shreya A. Raghavan · 2023 to 2026
$928k
Primary cilia as regulators of vascular stability during embryonic developmentK99HL171944 · NHLBI · WASHINGTON UNIVERSITY · PI WILSON-COLIJN, SARAH ANN · 2024 to 2025
$217k
Cancer Prevention and Research Institute of Texas (CPRIT) RP230204National Institutes of Health (NIH) R35GM137976National Institutes of Health (NIH) R37CA269224NCI NIH HHS R37 CA269224NHLBI NIH HHS K99 HL171944NIGMS NIH HHS R35 GM137976
6 · The paper itself

Abstract

Colorectal cancer tumors start as polyps on the inner lining of the colorectum, in which they are exposed to the mechanics of peristalsis. Our previous work leveraged a custom-built peristalsis bioreactor to demonstrate that colonic peristalsis led to cancer stem cell enrichment in colorectal cancer cells. However, this malignant mechanotransductive response was confined to select colorectal cancer lines that harbored an oncogenic mutation in the Kirsten rat sarcoma virus (KRAS) gene. In this study, we explored the involvement of activating KRAS mutations on peristalsis-associated mechanotransduction in colorectal cancer. Peristalsis enriched cancer stem cell marker Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) in KRAS mutant lines in a Wnt ligand-independent manner. Conversely, LGR5 enrichment in wild-type KRAS lines exposed to peristalsis were minimal. LGR5 enrichment downstream of peristalsis translated to increased tumorigenicity in vivo. Differences in mechanotransduction were apparent via unbiased gene set enrichment analysis, in which many unique pathways were enriched in wild-type versus mutant lines. Peristalsis also triggered β-catenin nuclear localization independent of Wnt ligands, particularly in KRAS mutant lines. The involvement of KRAS was validated via gain and loss of function strategies. Peristalsis-induced β-catenin activation and LGR5 enrichment depended on the activation of the MEK/ERK cascade. Taken together, our results demonstrated that oncogenic KRAS mutations conferred a unique peristalsis-associated mechanotransduction response to colorectal cancer cells, resulting in cancer stem cell enrichment and increased tumorigenicity. These mechanosensory connections can be leveraged in improving the sensitivity of emerging therapies that target oncogenic KRAS. Implications: Oncogenic KRAS empowers colorectal cancer cells to harness the mechanics of colonic peristalsis for malignant gain independent of other cooperating signals.

Indexed as

Colorectal NeoplasmsMechanotransduction, CellularPeristalsisProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorHumansMiceMutationNeoplastic Stem CellsReceptors, G-Protein-CoupledKRAS protein, humanLGR5 protein, humanProto-Oncogene Proteins p21(ras)Receptors, G-Protein-Coupled

Identifiers

PMID39485528
PMCPMC11802306

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.