Evidence map›Paper›PMID 34965432›Full record

ArticleCell reports2021

Substratum stiffness regulates Erk signaling dynamics through receptor-level control.

Payam E Farahani, Sandra B Lemke, Elliot Dine, Giselle Uribe, Jared E Toettcher, Celeste M Nelson

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

29 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026
    Review
  5. Review
  6. Review
  7. Engineered calcium-regulated affinity protein for efficient internalization and lysosomal toxin delivery.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Emerging roles and mechanisms of ERK pathway mechanosensing.Cellular and molecular life sciences : CMLS · 2023
    Review
  19. Article
  20. Optogenetic clustering and membrane translocation of the BcLOV4 photoreceptor.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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

6 authors at 1 institution in 1 country.

Payam E FarahaniDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Sandra B LemkeDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Elliot DineDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Giselle UribeDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Jared E ToettcherDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: toettcher@princeton.edu.
Celeste M NelsonDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: celesten@princeton.edu.
Princeton University · US

Funding

Engineered Invasive Human Breast Tumors with Integrated Capillaries and LymphaticsU01CA214292 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI NELSON, CELESTE M, TIEN, JOE Y · 2017 to 2021
$3.2M
Harnessing optogenetics to diagnose and therapeutically rewire cancer cell signalingDP2EB024247 · NIBIB · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2016 to 2016
$2.4M
Biophysical and Biochemical Effects of the ECM on Breast Epithelial CellsR01CA187692 · NCI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M, RADISKY, DEREK C · 2015 to 2019
$2.1M
Mechanical Regulation of Mesenchyme and Mammalian Lung DevelopmentR01HL120142 · NHLBI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M · 2014 to 2017
$1.6M
Mechanical regulation of branching morphogenesisR21HL110335 · NHLBI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M · 2011 to 2012
$443k
Exogenous Fluid Forces and Branching of the Mammalian LungR21HL118532 · NHLBI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M · 2014 to 2015
$442k
NCI NIH HHS R01 CA187692NCI NIH HHS U01 CA214292NHLBI NIH HHS R01 HL120142NHLBI NIH HHS R21 HL110335NHLBI NIH HHS R21 HL118532NIBIB NIH HHS DP2 EB024247
6 · The paper itself

Abstract

The EGFR/Erk pathway is triggered by extracellular ligand stimulation, leading to stimulus-dependent dynamics of pathway activity. Although mechanical properties of the microenvironment also affect Erk activity, their effects on Erk signaling dynamics are poorly understood. Here, we characterize how the stiffness of the underlying substratum affects Erk signaling dynamics in mammary epithelial cells. We find that soft microenvironments attenuate Erk signaling, both at steady state and in response to epidermal growth factor (EGF) stimulation. Optogenetic manipulation at multiple signaling nodes reveals that intracellular signal transmission is largely unaffected by substratum stiffness. Instead, we find that soft microenvironments decrease EGF receptor (EGFR) expression and alter the amount and spatial distribution of EGF binding at cell membranes. Our data demonstrate that the mechanical microenvironment tunes Erk signaling dynamics via receptor-ligand interactions, underscoring how multiple microenvironmental signals are jointly processed through a highly conserved pathway that regulates tissue development, homeostasis, and disease progression.

Indexed as

Cellular MicroenvironmentCell MovementCells, CulturedErbB ReceptorsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFemaleHumansMammary Glands, HumanPhosphorylationSignal TransductionEGFR protein, humanErbB ReceptorsExtracellular Signal-Regulated MAP KinasesMAP kinasemorphodynamicsreceptor tyrosine kinasesignaling dynamicstissue mechanics

Identifiers

PMID34965432
PMCPMC8756379
OpenAlexW4200291185

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.