Cited by 393Cancer, Hypoxia, and MetabolismCellular Mechanics and InteractionsCancer, Lipids, and Metabolism

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

Open access
Bertero, Thomas, Oldham, William M., Grasset, Eloise M., Bourget, Isabelle, Boulter, Etienne, Pisano, Sabrina, Hofman, Paul, Bellvert, Floriant +7 more·2019·Cell Metabolism

Abstract

Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino acid flux within the tumor niche. Specifically, we demonstrate a metabolic crosstalk between CAF and cancer cells in which CAF-derived aspartate sustains cancer cell proliferation, while cancer cell-derived glutamate balances the redox state of CAFs to promote ECM remodeling. Collectively, our findings link mechanical stimuli to dysregulated tumor metabolism and thereby highlight a new metabolic network within tumors in which diverse fuel sources are used to promote growth and aggressiveness. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2018.09.012

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Williamson K, Moeendarbary P, Charras G E, (2013). Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 15, 637– 646. 23708000 PMC3836234

Cited by

Sorted by citations

Authors
Bertero, T., Oldham, W. M., Grasset, E. M., Bourget, I., Boulter, E., Pisano, S., Hofman, P., Bellvert, F., Meneguzzi, G., Bulavin, D. V., Estrach, S., Feral, C. C., Chan, S. Y., Bozec, A., & Gaggioli, C.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Brigham and Women's Hospital (US)
  • University of Pittsburgh Medical Center (US)
Corresponding author
Bertero, Thomas
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2019-01
Volume
29
Issue
1
Pages
124-140.e10
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2895250239
Cited by
393
References
56
Citations by year
2026: 45 · 2025: 56 · 2024: 71 · 2023: 56 · 2022: 53 · 2021: 49 · 2020: 39 · 2019: 23
FWCI
8.39
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, cc-by-nc)
Funders
  • Ligue Contre le Cancer
  • Agence Nationale de la Recherche (ANR-11-LABX-0028-01)
  • Association pour la Recherche sur le Cancer (PJA20131200325)
  • American Heart Association (HL128802, 18EIA33900027)
  • Canceropôle PACA
  • Fondation pour la Recherche Médicale (DEQ20180339183)
  • National Institutes of Health (HL 138437, UH2 TR002073, HL 122596, R01 HL124021)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
extracellular matrix stiffness, mechanotransduction, glycolysis, glutamine metabolism, amino acid availability, cancer-associated fibroblasts, tumor cell proliferation, aspartic acid, glutamate, redox state, extracellular matrix remodeling, cancer metabolism, metabolic crosstalk, cancer drug targets
MeSH terms
Cancer-Associated Fibroblasts, YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Animals, Aspartic Acid, Breast Neoplasms, Carcinoma, Cell Line, Extracellular Matrix, Female, Head and Neck Neoplasms, Humans, Lung Neoplasms, Mice, Inbred BALB C, Transcription Factors, Trans-Activators, Glutamic Acid, Adaptor Proteins, Signal Transducing, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review