Metabolic Salvage and Acyl-chain Remodeling Support Glycosphingolipid Synthesis within the PDAC Tumor Microenvironment
. We use targeted pharmacological modulators to highlight the importance of recycling pathways and metabolic redundancies which mitigate changes in lipid abundances. Finally, we leverage targeted lipid fluxomics and the distinct ganglioside and globoside profiles of tumor and stromal cells, respectively, to demonstrate the role of the lipid kinase PIKfyve in supporting ganglioside homeostasis via sialic acid and ceramide salvage. These data establish application of MFA to slice cultures of PDAC tumors as an effective approach for assessing metabolic mechanisms and therapeutic responses within an intact TME.
Authors
- Tae Gyu Oh (ORCID: https://orcid.org/0000-0002-2756-3546)
- Kristina Peck
- Hervé Tiriac (ORCID: https://orcid.org/0000-0001-5039-6750)
- Jonathan Weitz (ORCID: https://orcid.org/0000-0003-0216-7990)
- Christian M. Metallo (ORCID: https://orcid.org/0000-0003-2404-3040)
- Dannielle D. Engle (ORCID: https://orcid.org/0000-0003-1876-7675)
- Casie S. Kubota (ORCID: https://orcid.org/0000-0003-2323-7409)
- Andrew M. Lowy (ORCID: https://orcid.org/0000-0002-7106-0735)
- Ethan L. Ashley (ORCID: https://orcid.org/0009-0004-1620-3811)
- Maureen L. Ruchhoeft (ORCID: https://orcid.org/0009-0000-6643-5566)
- Elaine Zhao
- Anna S Trimble (ORCID: https://orcid.org/0009-0009-0982-1343)
- Woncheol Jung (ORCID: https://orcid.org/0000-0002-5473-9463)
- Satoshi Ogawa
Institutions
- Salk Institute for Biological Studies (US)
- UC San Diego Health System (US)
- University of California San Diego (US)
- La Jolla Bioengineering Institute (US)
- University of Oklahoma Health Sciences Center (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-17
- DOI
- https://doi.org/10.64898/2026.04.14.718544
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00