Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions
Open accessAbstract
Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo . Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.
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Macropinocytosis is a non-substrate-specific fluid-phase uptake process engaged by oncogenic KRAS signaling.
“macropinocytosis is a non-substrate specific fluid phase uptake process engaged by oncogenic KRAS signaling229”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [229]
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- Authors
- Olivares, O., Mayers, J. R., Gouirand, V., Torrence, M. E., Gicquel, T., Borge, L., Lac, S., Roques, J., Lavaut, M.-N., Berthezène, P., Rubis, M., Secq, V., Garcia, S., Moutardier, V., Lombardo, D., Iovanna, J. L., Tomasini, R., Guillaumond, F., Vander Heiden, M. G., & Vasseur, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Inserm (FR)
- Corresponding author
- Vasseur, Sophie
- ORCID
- Venue
- Nature Communications
- Published
- 2017-07-07
- Volume
- 8
- Issue
- 1
- Pages
- 16031-16031
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5504351
- OpenAlex
- W2726164542
- Cited by
- 413
- References
- 60
- Citations by year
- 2026: 22 · 2025: 53 · 2024: 46 · 2023: 51 · 2022: 60 · 2021: 72 · 2020: 51 · 2019: 29 · 2018: 22 · 2017: 6
- FWCI
- 13.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- Lustgarten Foundation
- University of Glasgow
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Fondation de France
- Institut National Du Cancer
- Direction Générale de l’offre de Soins
- Stand Up To Cancer
- Ludwig Center for Molecular Oncology
- Ludwig Center at Harvard
- National Cancer Institute (F30CA183474, P30CA014051)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- pancreatic ductal adenocarcinoma, extracellular matrix, nutrient limitation, cancer metabolism, proline oxidase, cell proliferation, tumor microenvironment, metabolic flexibility, collagen fragments
- MeSH terms
- Animals, Biological Transport, Cell Survival, Collagen, Extracellular Matrix, Humans, Male, Mice, Transgenic, Neoplasm Transplantation, Pancreatic Neoplasms, Proline, Procollagen-Proline Dioxygenase, Proline Oxidase, Signal Transduction, Gene Expression Regulation, Neoplastic, Matrix Metalloproteinase 9, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Proliferation, Mice, Matrix Metalloproteinase 13
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 ›
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