ArticleNature communications2016
Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer.
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Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
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58 citing papers in PubMed, 84 citations in OpenAlex.
- The glycobiology of prostate cancer: an update.Oncogene · 2026Review
- Carbohydrate responsive element binding protein promotes colorectal carcinogenesis via Wnt/β-catenin pathway.Oncogene · 2026Article
- Integrative transcriptomic and single-cell analysis reveals metabolic reprogramming and hexosamine biosynthesis-mediated tumor microenvironment remodeling in prostate cancer.Discover oncology · 2026Article
- The hexosamine biosynthetic pathway alters the cytoskeleton to modulate cell proliferation and migration in aggressive prostate cancer.Cell communication and signaling : CCS · 2026Article
- Downregulation of GNPNAT1 impaired proliferation and correlates with immune infiltration in lung adenocarcinoma.Discover oncology · 2026Article
- ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1.Oncology research · 2026Article
- NBPF1 acts as a tumor suppressor in prostate cancer by regulating the PI3K/AKT pathway.Archives of medical science : AMS · 2026Article
- Unraveling the role of ChREBP in lung adenocarcinoma: Expression, regulatory networks, and potential functional impact.PloS one · 2026Article
- Proteome-wide association study of prostate cancer risk across populations.Nature communications · 2025Article
- GNPNAT1 acts as a prognostic biomarker associated with immune infiltration in lung adenocarcinoma and promotes the proliferation and invasion of cancer cells.Discover oncology · 2025Article
- Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade.Clinical and translational medicine · 2025Article
- Metabolic adaptations in prostate cancer.British journal of cancer · 2024Review
- GNPNAT1 Serves as a Prognostic Biomarker Correlated with Immune Infiltration and Promotes Cancer Cell Metastasis through Stabilization of Snai2 in Lung Adenocarcinoma.Biomedicines · 2024Article
- Article
- Androgen-repressed lncRNA LINC01126 drives castration-resistant prostate cancer by regulating the switch between O-GlcNAcylation and phosphorylation of androgen receptor.Clinical and translational medicine · 2024Article
- Article
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- Current knowledge and potential intervention of hexosamine biosynthesis pathway in lung cancer.World journal of surgical oncology · 2023Review
- Regulatory roles of NAT10 in airway epithelial cell function and metabolism in pathological conditions.Cell biology and toxicology · 2023Article
- GNPNAT1 promotes the stemness of breast cancer and serves as a potential prognostic biomarker.Oncology reports · 2023Article
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Authors and funding
36 authors at 7 institutions in 2 countries.
Akash K KaushikDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Ali ShojaieDepartment of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
Katrin PanzittDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Rajni SonavaneDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Harene VenghatakrishnanComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Mohan ManikkamDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Alexander ZaslavskyComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Vasanta PutluriDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Vihas T VasuDepartment of Zoology, Maharaja Sayajirao University of Baroda, Vadodara 390002, India.
Yiqing ZhangDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Ayesha S KhanCenter for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
Stacy LloydDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Adam T SzafranDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Subhamoy DasguptaDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.ORCID 0000-0001-7167-908X
David A BaderDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Fabio StossiDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Hangwen LiComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Susmita SamantaDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Xuhong CaoComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Efrosini TsoukoCenter for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
Shixia HuangDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Daniel E FrigoCenter for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
Lawrence ChanDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Dean P EdwardsDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Benny A KaipparettuDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Nicholas MitsiadesDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Nancy L WeigelDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Michael ManciniDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Sean E McGuireDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Rohit MehraComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Michael M IttmannDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Arul M ChinnaiyanComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nagireddy PutluriDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Ganesh S PalapattuComprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
George MichailidisDepartment of Statistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Arun SreekumarDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
Baylor College of Medicine · USUniversity of Michigan · USUniversity of Houston · USHouston Methodist · USHoward Hughes Medical Institute · USMaharaja Sayajirao University of Baroda · INUniversity of Washington · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MTissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI James Versalovic · 2001 to 2026
$28.3MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6MTRANSGENIC MOUSE MODELS TO STUDY OVARIAN FUNCTIONU54HD007495 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI MATZUK, MARTIN M. · 1998 to 2013
$19.9MEpitomic Biomarkers of Prostate CancerU01CA111275 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, RUBIN, MARK A. · 2004 to 2015
$6.8MGenetic & Metabolic Dissection of the CaMKKbeta Signaling Axis in Prostate CancerR01CA184208 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FRIGO, DANIEL EDWARD · 2015 to 2019
$1.9MMETABOLOMIC PROFILING AND BIOLOGIC BASIS OF RACIAL DISPARITY IN PROSTATE CANCERU01CA167234 · NCI · BAYLOR COLLEGE OF MEDICINE · PI PALAPATTU, GANESH S, SREEKUMAR, ARUN · 2012 to 2016
$1.9MMachine Learning Tools for Discovery and Analysis of Active Metabolic PathwaysR01GM114029 · NIGMS · UNIVERSITY OF WASHINGTON · PI SHOJAIE, ALI · 2016 to 2020
$1.7MGROWTH AND DIFFERENTIATION IN EUKARYOTEST32HD007495 · NICHD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI KINTNER, CHRISTOPHER ROBERT · 1995 to 2009
$1.6MIntegrative Metabolomics of Prostate Cancer ProgressionR01CA133458 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SREEKUMAR, ARUN · 2008 to 2012
$1.6MIntegromics with Application to Prostate Cancer ProgressionRC1CA145444 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MICHAILIDIS, GEORGE · 2009 to 2010
$999kStatistical Methods for Network-Based Integrative Analysis of CVD Epigenetic DataK01HL124050 · NHLBI · UNIVERSITY OF WASHINGTON · PI SHOJAIE, ALI · 2016 to 2020
$693kNCI NIH HHS F30 CA196108NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA133458NCI NIH HHS R01 CA184208NCI NIH HHS R21 CA173150NCI NIH HHS R21 CA179720NCI NIH HHS R21 CA205257NCI NIH HHS RC1 CA145444NCI NIH HHS U01 CA111275NCI NIH HHS U01 CA167234NICHD NIH HHS P30 HD007495NICHD NIH HHS T32 HD007495NIDDK NIH HHS P30 DK056338
Abstract
The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is found to be significantly decreased in CRPC compared with localized prostate cancer (PCa). Genetic loss-of-function of GNPNAT1 in CRPC-like cells increases proliferation and aggressiveness, in vitro and in vivo. This is mediated by either activation of the PI3K-AKT pathway in cells expressing full-length androgen receptor (AR) or by specific protein 1 (SP1)-regulated expression of carbohydrate response element-binding protein (ChREBP) in cells containing AR-V7 variant. Strikingly, addition of the HBP metabolite UDP-N-acetylglucosamine (UDP-GlcNAc) to CRPC-like cells significantly decreases cell proliferation, both in-vitro and in animal studies, while also demonstrates additive efficacy when combined with enzalutamide in-vitro. These observations demonstrate the therapeutic value of targeting HBP in CRPC.
Indexed as
AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell LineHexosaminesHumansMaleMiceMice, SCIDPhosphatidylinositol 3-KinasesProstatic Neoplasms, Castration-ResistantProto-Oncogene Proteins c-aktBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsHexosaminesMLXIPL protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt
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