Role of SCAP in regulation of pancreatic homeostasis, pancreatitis, and tumorigenesis
mice had rapid progressive loss of acinar cells, acinar-ductal metaplasia (ADM), infiltration of adipose cells, increased fibrosis, and infiltration of immune cells, indicative of chronic pancreatitis. Single cell RNA sequencing indicated that loss of SCAP suppressed SREBP-dependent transcriptional programs in endocrine and exocrine precursors, but was associated with enhanced SREBP2 activity in fibroblastic populations, compatible with formation of a pro-tumorigenic tumor microenvironment. Together, these results implicate lipid metabolism via SCAP-SREBP signaling as an important metabolic regulator of acinar-ductal differentiation and pancreatic carcinogenesis.
Authors
- Erica A. Golemis (ORCID: https://orcid.org/0000-0003-3618-3673)
- Valerii A. Pavlov (ORCID: https://orcid.org/0000-0002-8139-9978)
- Edna Cukierman (ORCID: https://orcid.org/0000-0002-1452-9576)
- Nathaniel W. Snyder (ORCID: https://orcid.org/0000-0001-5643-8747)
- Adam G. Chatoff (ORCID: https://orcid.org/0000-0002-7954-9527)
- Anna C. Lilly (ORCID: https://orcid.org/0000-0002-0385-6088)
- Kathy Q. Cai (ORCID: https://orcid.org/0000-0002-6034-3377)
- Igor Astsaturov (ORCID: https://orcid.org/0000-0002-8613-1890)
- Shabnam Pirestani
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- Fox Chase Cancer Center (US)
- Drexel University (US)
- Temple University (US)
Publication Details
- Journal
- Oncogene
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1038/s41388-026-03784-y
- Primary Topic
- Cancer, Lipids, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Cancer Institute