2 options
Hexosamine salvage in pancreatic cancer / Sydney L. Campbell.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Campbell, Sydney L., author.
- Language:
- English
- Subjects (All):
- Cellular biology.
- Biochemistry.
- DNA methylation.
- Epigenetics.
- Kinases.
- Metabolites.
- Mutation.
- Oncology.
- Cell and molecular biology--Penn dissertations.
- Penn dissertations--Cell and molecular biology.
- Local Subjects:
- Cellular biology.
- Biochemistry.
- DNA methylation.
- Epigenetics.
- Kinases.
- Metabolites.
- Mutation.
- Oncology.
- Cell and molecular biology--Penn dissertations.
- Penn dissertations--Cell and molecular biology.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (110 pages)
- Contained In:
- Dissertations Abstracts International 83-03B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Tumors of many types exhibit aberrant glycosylation, which can impact cancer progression and therapeutic responses. The hexosamine biosynthesis pathway (HBP) branches from glycolysis at fructose-6-phosphate to synthesize uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a major substrate for glycosylation in the cell. HBP enzyme gene expression is elevated in pancreatic ductal adenocarcinoma (PDA), and studies have pointed to the potential significance of the HBP as a therapeutic target. Yet, the PDA tumor microenvironment is nutrient poor, and adaptive nutrient acquisition strategies support tumorigenesis. Here, we identify that pancreatic cancer cells salvage GlcNAc via N-acetylglucosamine kinase (NAGK), particularly under glutamine limitation. Glutamine deprivation suppresses de novo HBP flux and triggers upregulation of NAGK. NAGK expression is elevated in human PDA. NAGK deletion forces PDA cells to rely on de novo UDP-GlcNAc synthesis and impairs tumor growth in mice. Together, these data identify an important role for NAGK-dependent hexosamine salvage in supporting PDA tumor growth.
- Notes:
- Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
- Advisors: Wellen, Kathryn E.; Committee members: Stanger, Ben Z.; Koumenis, Costas; Tong, Wei; Reginato, Mauricio.
- Department: Cell and Molecular Biology.
- Ph.D. University of Pennsylvania 2021.
- Local Notes:
- School code: 0175
- ISBN:
- 9798535569444
- Access Restriction:
- Restricted for use by site license.
- This item must not be sold to any third party vendors.
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