Evidence map›Paper›PMID 40796929›Full record

ArticleScientific reports2025

Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.

Kenneth K Y Ho, Johanna M Buschhaus, Anne Zhang, Alyssa C Cutter, Brock A Humphries, Gary D Luker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 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. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Kenneth K Y HoCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Johanna M BuschhausCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Anne ZhangCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Alyssa C CutterCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Brock A HumphriesCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. brhu@med.umich.edu.
Gary D LukerCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.

Funding

Interstitial Fluid Flow Regulates Glioma Cell InvasionR37CA222563 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI MUNSON, JENNIFER M · 2018 to 2024
$4.0M
University of Michigan Quantitative Co-Clinical Imaging Research ResourceU24CA237683 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHENEVERT, THOMAS L, LUKER, GARY D · 2019 to 2023
$3.1M
Imaging Disease Heterogeneity and Response to Therapy in MyelofibrosisR01CA238023 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D, ROSS, BRIAN D. · 2019 to 2023
$3.1M
Integrators of Metastatic PotentialR01CA238042 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, LUKER, GARY D · 2019 to 2023
$2.3M
A High Throughput Human Tumor Modeling Technology for Cancer Drug DiscoveryR33CA225549 · NCI · UNIVERSITY OF AKRON · PI LUKER, GARY D, TAVANA, HOSSEIN · 2019 to 2021
$1.4M
Sensing and modulating the chemokine environment with synthetic cellsR21AI173559 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, ALLEN PO-CHIH, LUKER, GARY D · 2023 to 2024
$429k
National Science Foundation 2140104NCI NIH HHS R01 CA238023NCI NIH HHS R01 CA238042NCI NIH HHS R33 CA225549NCI NIH HHS R37 CA222563NCI NIH HHS U24 CA237683NIAID NIH HHS R21 AI173559NIH HHS R01CA238042U.S. Department of Defense W81XWH2210120
6 · The paper itself

Abstract

Biophysical properties of the extracellular matrix (ECM), such as mechanical stiffness, directly regulate behaviors of cancer cells linked to cancer initiation and progression. Cells sense and respond to ECM stiffness in the context of dynamic changes in biochemical inputs, such as growth factors and chemokines. While commonly studied as isolated inputs, mechanisms by which combined effects of mechanical stiffness and biochemical factors affect functions of cancer cells remain poorly defined. Using a combination of elastically supportive surface (ESS) culture dishes with defined stiffnesses and single-cell imaging, we report here that culturing cells on a stiff (28 kPa) versus soft (1.5 kPa) substrate increases CXCR4 and EGFR expression and promotes greater ligand-dependent internalization of CXCR4. In addition to increased CXCR4 expression, a stiff ECM also increases basal activation of Akt and ERK as well as signaling through these kinases in response to CXCL12-α and EGF and promotes migration of triple negative breast cancer (TNBC) cells. These data implicate receptor dynamics as a key mediator of Akt and ERK signaling as a mechanism for adverse effects of enhanced ECM stiffness on disease progression in TNBC.

Indexed as

Extracellular MatrixReceptors, CXCR4Signal TransductionTriple Negative Breast NeoplasmsCell Line, TumorCell MovementChemokine CXCL12ErbB ReceptorsFemaleHumansProto-Oncogene Proteins c-aktChemokine CXCL12CXCR4 protein, humanErbB ReceptorsProto-Oncogene Proteins c-aktReceptors, CXCR4AktCXCR4ERKExtracellular matrixSignaling dynamicsTriple-negative breast cancer

Identifiers

PMID40796929
PMCPMC12343888

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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.