ORCID
0009-0009-0489-8245 (Brown)
Document Type
Article
Publication Date
2025
DOI
10.1038/s41598-025-19722-z
Publication Title
Scientific Reports
Volume
15
Issue
1
Pages
35811 (1-9)
Abstract
What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with pro-tumorigenic proteins like plasma gelsolin (pGSN), with D-peptides modulating these interactions. These findings underscore DCLK1’s non-kinase functions as a therapeutic target and highlight novel avenues for developing precision treatments aimed at halting cancer progression and improving patient outcomes.
Rights
© 2025 The Authors.
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Data Availability
Article states: "All data are available in the main text or the supplementary materials."
Original Publication Citation
Moore, L. L., Qu, D., Chandrekesan, P., Pitts, K., May, R., Anderson, B. E., Brown, M. L., & Houchen, C. W. (2025). A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth. Scientific Reports, 15(1), 1-9, Article 35811. https://doi.org/10.1038/s41598-025-19722-z
Repository Citation
Moore, L. L., Qu, D., Chandrekesan, P., Pitts, K., May, R., Anderson, B. E., Brown, M. L., & Houchen, C. W. (2025). A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth. Scientific Reports, 15(1), 1-9, Article 35811. https://doi.org/10.1038/s41598-025-19722-z
Supplementary Material 1
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Medical Pathology Commons, Oncology Commons, Pharmacy and Pharmaceutical Sciences Commons