ORCID ID
Graduation Date
Summer 8-15-2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Programs
Cancer Research
First Advisor
Dr. Jixin Dong
Second Advisor
Dr. Nick T Woods
Third Advisor
Dr. Ying Yan
MeSH Headings
Sphingosine-1-Phosphate, Sphingosine-Phosphate Phosphatase, Pancreatic Neoplasms, Valproic Acid, Histone Deacetylase Inhibitors, Cell Movement
Abstract
Sphingosine-1-phosphate phosphatase 1 (SGPP1) is a key regulator of sphingolipid metabolism that facilitates the degradation of sphingosine-1-phosphate (S1P), a bioactive lipid mediator with significant influence on key cellular processes including proliferation, migration, invasion, and apoptosis. In pancreatic cancer, the dysregulation of SGPP1 expression may play a part in enhancing tumor aggressiveness and chemo-resistance through disrupting the balance of S1P. Most notably, elevated intracellular and nuclear levels of sphingosine-1-phosphate (S1P) have been found to function as endogenous histone deacetylase inhibitors (HDACis), replicating the action of pharmacologic HDACis such as valproic acid (VPA). As VPA is an FDA-approved HDACi, this is one enticing therapeutic approach to pharmacologically replicate the result of SGPP1 knockdown, thereby allowing S1P to accumulate within cells.
Increased nuclear S1P, either as a result of SGPP1 inhibition or VPA treatment, was associated with reduced proliferation, migration, and invasion of pancreatic cancer cells and thus an oncogenic function via epigenetic reprogramming. In this case, valproic acid can serve both as a tool for investigating the role of SGPP1 and as a drug candidate in pancreatic cancer.
This thesis investigates the functional relationship between valproic acid treatment and SGPP1 expression in pancreatic cancer cells. Through the utilization of a series of assays, including proliferation, wound healing, migration, and invasion, we determined the phenotypic effect of suppressed SGPP1 on cancer cell proliferation. In general, these experiments aim to explain how pharmacological disruption of sphingolipid metabolism can impact tumor growth and shed light on novel therapeutic strategies targeting SGPP1 pathways in pancreatic cancer.
Recommended Citation
Abbasi, Hamed, "Targeting SGPP1 in Pancreatic Cancer: Valproic Acid as a Potential Therapeutic via HDAC Inhibition and S1P Pathway Modulation" (2025). Theses & Dissertations. 977.
https://digitalcommons.unmc.edu/etd/977
Included in
Laboratory and Basic Science Research Commons, Medical Cell Biology Commons, Molecular Genetics Commons, Oncology Commons, Other Medical Sciences Commons
Comments
2025 Copyright, the authors