Evidence map›Paper›PMID 39302966›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Genetic variation drives cancer cell adaptation to ECM stiffness.

Ting-Ching Wang, Suchitaa Sawhney, Daylin Morgan, Richard L Bennett, Richa Rashmi, Marcos R Estecio, Amy Brock, Irtisha Singh, Charles F Baer, Jonathan D Licht and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

11 authors.

Ting-Ching WangArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843.
Suchitaa SawhneyDepartment of Biomedical Engineering, Texas A&M University, College Station, TX 77843.
Daylin MorganDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712.
Richard L BennettDivision of Hematology and Oncology, University of Florida Health Cancer Center, Gainesville, FL 32610.ORCID 0000-0002-0243-2443
Richa RashmiDepartment of Cell Biology and Genetics, Texas A&M University, Bryan, TX 77807.
Marcos R EstecioDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Amy BrockDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712.
Irtisha SinghDepartment of Biomedical Engineering, Texas A&M University, College Station, TX 77843.ORCID 0000-0002-9460-3587
Charles F BaerDepartment of Biology, University of Florida, Gainesville, FL 32611.ORCID 0000-0002-0140-5814
Jonathan D LichtDivision of Hematology and Oncology, University of Florida Health Cancer Center, Gainesville, FL 32610.
Tanmay P LeleArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843.

Funding

Nuclear Dysfunction in Cancer: The Role of Mechanical Stresses Transmittedby the LINC ComplexU01CA225566 · NCI · UNIVERSITY OF FLORIDA · PI LELE, TANMAY P. · 2020 to 2024
$3.1M
Instability of Cancer Cell States in Tumor progression (ICCS)R01CA255536 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI BROCK, AMY, HUANG, SUI · 2021 to 2025
$2.5M
The Allee Effect in Tumor InitiationR01CA226258 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI BROCK, AMY, HUANG, SUI · 2018 to 2022
$2.3M
Using label-free Raman microscopy to predict therapeutic resistance of TNBC cellsU01CA253540 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI BROCK, AMY, YANKEELOV, THOMAS E · 2020 to 2024
$2.1M
Investigating epigenetic mechanisms of cancerR50CA293837 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI Richard L Bennett · 2024 to 2026
$528k
Cancer Prevention and Research Institute of Texas (CPRIT) RR200043NCI NIH HHS R01 CA226258NCI NIH HHS R01 CA255536NCI NIH HHS R50 CA293837NCI NIH HHS U01 CA225566NCI NIH HHS U01 CA253540
6 · The paper itself

Abstract

The progression of many solid tumors is accompanied by temporal and spatial changes in the stiffness of the extracellular matrix (ECM). Cancer cells adapt to soft and stiff ECM through mechanisms that are not fully understood. It is well known that there is significant genetic heterogeneity from cell to cell in tumors, but how ECM stiffness as a parameter might interact with that genetic variation is not known. Here, we employed experimental evolution to study the response of genetically variable and clonal populations of tumor cells to variable ECM stiffness. Proliferation rates of genetically variable populations cultured on soft ECM increased over a period of several weeks, whereas clonal populations did not evolve. Tracking of DNA barcoded cell lineages revealed that soft ECM consistently selected for the same few variants. These data provide evidence that ECM stiffness exerts natural selection on genetically variable tumor populations. Soft-selected cells were highly migratory, with enriched oncogenic signatures and unusual behaviors such as spreading and traction force generation on ECMs with stiffness as low as 1 kPa. Rho-regulated cell spreading was found to be the directly selected trait, with yes-associated protein 1 translocation to the nucleus mediating fitness on soft ECM. Overall, these data show that genetic variation can drive cancer cell adaptation to ECM stiffness.

Indexed as

Extracellular MatrixGenetic VariationAdaptation, PhysiologicalCell Line, TumorCell MovementCell ProliferationHumansNeoplasmscancerECM stiffnessmechanoadaptationmechanobiology

Identifiers

PMID39302966
PMCPMC11441511

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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.