气候变化领域集成服务门户(CCPortal): UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth

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DOI	10.1073/pnas.2103592118
	UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth
	Wolfe A.L.; Zhou Q.; Toska E.; Galeas J.; Ku A.A.; Koche R.P.; Bandyopadhyay S.; Scaltriti M.; Lebrilla C.B.; McCormick F.; Kim S.E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Glycogen; N-glycosylation; PDAC; UDP-glucose; UGP2
语种	英语
scopus关键词	glycogen; TEAD1 protein, human; uridine triphosphate glucose 1 phosphate uridylyltransferase; YAP1 protein, human; animal; biosynthesis; enzymology; experimental neoplasm; gene expression regulation; gene knockdown; genetics; glycosylation; human; metabolism; mouse; nude mouse; pancreas carcinoma; pancreas tumor; pathology; physiology; tumor cell line; Animals; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glycogen; Glycosylation; Humans; Mice; Mice, Nude; Neoplasms, Experimental; Pancreatic Neoplasms; TEA Domain Transcription Factors; UTP-Glucose-1-Phosphate Uridylyltransferase; YAP-Signaling Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251085
作者单位	Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158, United States; Department of Chemistry, University of California, Davis, CA 95616, United States; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, United States; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616, United States; Foods for Health Institute, University of California, Davis, CA 95616, United States; National Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, United States
推荐引用方式 GB/T 7714	Wolfe A.L.,Zhou Q.,Toska E.,et al. UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth[J],2021,118(31).
APA	Wolfe A.L..,Zhou Q..,Toska E..,Galeas J..,Ku A.A..,...&Kim S.E..(2021).UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Wolfe A.L.,et al."UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).