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UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth

  1. Author:
    Wolfe, Andrew L [ORCID]
    Zhou, Qingwen [ORCID]
    Toska, Eneda [ORCID]
    Galeas, Jacqueline [ORCID]
    Ku, Angel A [ORCID]
    Koche, Richard P [ORCID]
    Bandyopadhyay, Sourav [ORCID]
    Scaltriti, Maurizio [ORCID]
    Lebrilla, Carlito B [ORCID]
    McCormick, Frank [ORCID]
    Kim, Sung Eun [ORCID]

  2. Author Address

    Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158., Department of Chemistry, University of California, Davis, CA 95616., Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158., Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616., Foods for Health Institute, University of California, Davis, CA 95616., Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158; frank.mccormick@ucsf.edu sek19@korea.ac.kr., National Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701.,
    1. Year: 2021
    2. Date: Aug 03
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 118
    2. 31
  4. Type of Article: Article
  5. Article Number: e2103592118
  6. ISSN: 0027-8424
  1. Abstract:

    UDP-glucose pyrophosphorylase 2 (UGP2), the enzyme that synthesizes uridine diphosphate (UDP)-glucose, rests at the convergence of multiple metabolic pathways, however, the role of UGP2 in tumor maintenance and cancer metabolism remains unclear. Here, we identify an important role for UGP2 in the maintenance of pancreatic ductal adenocarcinoma (PDAC) growth in both in vitro and in vivo tumor models. We found that transcription of UGP2 is directly regulated by the Yes-associated protein 1 (YAP)-TEA domain transcription factor (TEAD) complex, identifying UGP2 as a bona fide YAP target gene. Loss of UGP2 leads to decreased intracellular glycogen levels and defects in N-glycosylation targets that are important for the survival of PDACs, including the epidermal growth factor receptor (EGFR). These critical roles of UGP2 in cancer maintenance, metabolism, and protein glycosylation may offer insights into therapeutic options for otherwise intractable PDACs. Copyright © 2021 the Author(s). Published by PNAS.

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External Sources

  1. View Full Text
  2. DOI: 10.1073/pnas.2103592118
  3. PMID: 34330832
  4. View record in Web of Science®
  5. WOS: 000685040600019
  6. PII : 2103592118

Library Notes

  1. Fiscal Year: FY2020-2021
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