The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
Open accessAbstract
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.
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Citations
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Metadata
- 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
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 29
- Issue
- 1
- Pages
- 124-140.e10
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6432652
- 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
- hybrid
- doi.org
- Licence
- 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
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