دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth.
المؤلفون: Wolfe AL; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158., Zhou Q; Department of Chemistry, University of California, Davis, CA 95616., Toska E; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Galeas J; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158., Ku AA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158.; Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158., Koche RP; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Bandyopadhyay S; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158.; Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158., Scaltriti M; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Lebrilla CB; Department of Chemistry, University of California, Davis, CA 95616.; Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616.; Foods for Health Institute, University of California, Davis, CA 95616., McCormick F; 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., Kim SE; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94158; frank.mccormick@ucsf.edu sek19@korea.ac.kr.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Aug 03; Vol. 118 (31).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Carcinoma, Pancreatic Ductal/*enzymology , Gene Expression Regulation, Enzymologic/*physiology , Gene Expression Regulation, Neoplastic/*physiology , Glycogen/*biosynthesis , Pancreatic Neoplasms/*enzymology , UTP-Glucose-1-Phosphate Uridylyltransferase/*metabolism, Animals ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Gene Knockdown Techniques ; Glycosylation ; Humans ; Mice ; Mice, Nude ; Neoplasms, Experimental ; Pancreatic Neoplasms/pathology ; TEA Domain Transcription Factors/genetics ; TEA Domain Transcription Factors/metabolism ; UTP-Glucose-1-Phosphate Uridylyltransferase/genetics ; YAP-Signaling Proteins/genetics ; YAP-Signaling Proteins/metabolism
مستخلص: 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.
Competing Interests: Competing interest statement: A.L.W. has received research funding from Oncogenuity. M.S. has received research funds from Puma Biotechnology, AstraZeneca, Daiichi-Sankyo, Immunomedics, Targimmune, and Menarini Ricerche. He is on the scientific advisory board of Menarini Ricerche and the Bioscience Institute, a cofounder of medendi.org, and an employee and stockholder of AstraZeneca. F.M. is a consultant for Daiichi-Sankyo, Pfizer, Amgen, BridgeBio, Olema, OPNA-IO, PMV, Quanta, and Remedy Plan and has received research funding from Daiichi-Sankyo.
(Copyright © 2021 the Author(s). Published by PNAS.)
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معلومات مُعتمدة: K99 CA226363 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R00 CA226363 United States CA NCI NIH HHS; R01 GM049077 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: N-glycosylation; PDAC; UDP-glucose; UGP2; glycogen
المشرفين على المادة: 0 (TEA Domain Transcription Factors)
0 (TEAD1 protein, human)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)
9005-79-2 (Glycogen)
EC 2.7.7.9 (UTP-Glucose-1-Phosphate Uridylyltransferase)
تواريخ الأحداث: Date Created: 20210731 Date Completed: 20211209 Latest Revision: 20220716
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8346792
DOI: 10.1073/pnas.2103592118
PMID: 34330832
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2103592118