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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere2103592118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number31
DOIs
Publication statusPublished - 2021 Aug 3
Externally publishedYes

Keywords

  • Glycogen
  • N-glycosylation
  • PDAC
  • UDP-glucose
  • UGP2

ASJC Scopus subject areas

  • General

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