ORCID ID
Graduation Date
Fall 12-19-2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Programs
Biochemistry & Molecular Biology
First Advisor
Moorthy Palanimuthu Ponnusamy, Ph.D.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent and aggressive type of pancreatic cancer, accounting for over 90% of pancreatic cancer cases. As of 2025, it has a 5-year survival rate of 13% and is predicted to become the 2nd leading cause of cancer-related deaths by the year 2030. Several key metabolites are altered in the progression of PDAC, including MUC16. MUC16 is a large transmembrane glycoprotein that aids in PDAC tumor cell growth and survival, immune evasion, metastasis, and chemoresistance. Additionally, MUC16 is involved in the metabolic rewiring of PDAC cells by improving motility and invasiveness and increasing glycolytic activity. A previous study indicates that MUC16 plays a role in the metabolic rewiring of PDAC cells, but the mechanisms of rewiring remain largely unknown. By utilizing both human and mouse cell lines, as well as mouse tissue samples, this study determined that MUC16 increases the glycolytic rate and decreases oxidative phosphorylation in PDAC cells, contributing to an increase in tumorigenic and metastatic potential. Furthermore, we identified that MUC16 alters the expression of hexokinase domain-containing 1 (HKDC1) through the upregulation of transcription factor MNT. Overall, this study suggests that MUC16’s regulation of MNT increases the expression of metabolic key enzyme HKDC1, resulting in an increased glycolytic rate in PDAC cells. Therefore, targeting HKDC1 may be a potential therapeutic option to slow the progression of PDAC and prolong the life expectancy of PDAC patients.
Recommended Citation
Thompson, Katelyn D., "MUC16 Rewires Metabolic Key Factors Through HKDC1 in the Progression of Pancreatic Ductal Adenocarcinoma" (2025). Theses & Dissertations. 1029.
https://digitalcommons.unmc.edu/etd/1029
Comments
2025 Copyright, the authors