دورية أكاديمية

Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.

التفاصيل البيبلوغرافية
العنوان: Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.
المؤلفون: Maurer HC; Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY., Garcia-Curiel A; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY., Holmstrom SR; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX., Castillo C; Department of Molecular & Integrative Physiology and Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI., Palermo CF; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY., Sastra SA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY., Andren A; Department of Molecular & Integrative Physiology and Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI., Zhang L; Department of Molecular & Integrative Physiology and Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI., Le Large TYS; Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands., Sagalovskiy I; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY., Ross DR; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY., Wong W; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY., Shaw K; Division of GI/Endocrine Surgery, Department of Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY., Genkinger J; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY., Manji GA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY., Iuga AC; Department of Pathology, Columbia University Irving Medical Center, New York, NY., Schmid RM; Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Johnson K; University of New Hampshire, Manchester, NH., Badgley MA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY., Lyssiotis CA; Department of Molecular & Integrative Physiology and Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI., Shah Y; Department of Molecular & Integrative Physiology and Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI., Califano A; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Darwin Therapeutics, New York, NY.; Chan Zuckerberg Biohub, New York, NY., Olive KP; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.; Columbia University Digestive and Liver Disease Research Center, Columbia University Irving Medical Center, New York, NY.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 22. Date of Electronic Publication: 2024 Jun 22.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: To identify drivers of malignancy in human pancreatic ductal adenocarcinoma (PDAC), we performed regulatory network analysis on a large collection of expression profiles from laser capture microdissected samples of PDAC and benign precursors. We discovered that BMAL2 plays a role in the initiation, progression, post resection survival, and KRAS activity in PDAC. Functional analysis of BMAL2 target genes led us to hypothesize that it plays a role in regulating the response to hypoxia, a critical but poorly understood feature of PDAC physiology. Knockout of BMAL2 in multiple human PDAC cell lines revealed effects on viability and invasion, particularly under hypoxic conditions. Loss of BMAL2 also affected glycolysis and other metabolic processes. We found that BMAL2 directly regulates hypoxia-responsive target genes. We also found that BMAL2 is necessary for the stabilization of HIF1A upon exposure to hypoxia, but destabilizes HIF2A under hypoxia. These data demonstrate that BMAL2 is a master transcriptional regulator of hypoxia responses in PDAC and may serve as a long-sought molecular switch that distinguishes HIF1A- and HIF2A-dependent modes of hypoxic metabolism.
معلومات مُعتمدة: P20 GM103506 United States GM NIGMS NIH HHS; P30 DK132710 United States DK NIDDK NIH HHS; R01 CA244931 United States CA NCI NIH HHS; P30 CA013696 United States CA NCI NIH HHS; R35 CA197745 United States CA NCI NIH HHS; R01 CA215607 United States CA NCI NIH HHS
تواريخ الأحداث: Date Created: 20230330 Latest Revision: 20240710
رمز التحديث: 20240710
مُعرف محوري في PubMed: PMC10055246
DOI: 10.1101/2023.03.19.533333
PMID: 36993718
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.03.19.533333