The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage Article Swipe
Georgios Efthymiou
,
Coralie Compare
,
Eugénie Lohmann
,
Paraskevi Kousteridou
,
Pierre Bertrand
,
Heather S. Carr
,
Issam Ben‐Sahra
,
Ivan Nemazanyy
,
Sarah-Simha Tubiana
,
Zainab Hussain
,
Pascal Finetti
,
François Bertucci
,
Ghislain Bidaut
,
Christophe Lachaud
,
Fabienne Guillaumond
,
Richard Tomasini
,
Sophie Vasseur
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.10.631286
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.10.631286
The excessive production of extracellular matrix (ECM) and the metabolic adaptations in pancreatic ductal adenocarcinoma (PDAC) contribute individually to enhanced chemoresistance, dramatic tumor progression and dismal patient survival. However, ECM-driven metabolic alterations that promote chemoresistance in PDAC are so far unexplored. Here, we use in-vitro -generated ECM bio-scaffolds that recapitulate cell-ECM interactions and induce broad metabolic alterations in PDAC cells. High-throughput integration of multi-omics datasets coupled with metabolic tracing showed that the ECM enhances the generation of guanylates in PDAC cells, the accumulation of which alleviates oxaliplatin-induced DNA damage, and boosts PDAC cell proliferation. These events are guided by the guanosine monophosphate (GMP)-producing enzymes Impdh and Gmps, the expression of which correlated with that of matrisomal and DNA repair genes in PDAC patient samples. We propose that targeting ECM-driven metabolic processes, like the enhanced Impdh activity, may be an effective therapeutic approach for PDAC patients that bypasses the negative side effects of direct targeting of the ECM itself.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.01.10.631286
- OA Status
- green
- Cited By
- 1
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406351629
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4406351629Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.01.10.631286Digital Object Identifier
- Title
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The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damageWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-01-14Full publication date if available
- Authors
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Georgios Efthymiou, Coralie Compare, Eugénie Lohmann, Paraskevi Kousteridou, Pierre Bertrand, Heather S. Carr, Issam Ben‐Sahra, Ivan Nemazanyy, Sarah-Simha Tubiana, Zainab Hussain, Pascal Finetti, François Bertucci, Ghislain Bidaut, Christophe Lachaud, Fabienne Guillaumond, Richard Tomasini, Sophie VasseurList of authors in order
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https://doi.org/10.1101/2025.01.10.631286Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.1101/2025.01.10.631286Direct OA link when available
- Concepts
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Oxaliplatin, Extracellular matrix, DNA damage, Pancreatic cancer, Cancer research, Extracellular, Chemistry, DNA, Cell biology, Cancer, Medicine, Biology, Internal medicine, Colorectal cancer, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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