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Pancreatic Neoplasms: HELP
Articles by Shigekazu Murakami
Based on 1 article published since 2010
(Why 1 article?)
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Between 2010 and 2020, Shigekazu Murakami wrote the following article about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article A Yap-Myc-Sox2-p53 Regulatory Network Dictates Metabolic Homeostasis and Differentiation in Kras-Driven Pancreatic Ductal Adenocarcinomas. 2019

Murakami, Shigekazu / Nemazanyy, Ivan / White, Shannon M / Chen, Hengye / Nguyen, Chan D K / Graham, Garrett T / Saur, Dieter / Pende, Mario / Yi, Chunling. ·Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA. · Institut National de la Santé et de la Recherche Médicale (INSERM) U1151, Institut Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, München, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Division of Translational Cancer Research, Heidelberg, Germany. · Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA. Electronic address: cy232@georgetown.edu. ·Dev Cell · Pubmed #31447265.

ABSTRACT: Employing inducible genetically engineered and orthotopic mouse models, we demonstrate a key role for transcriptional regulator Yap in maintenance of Kras-mutant pancreatic tumors. Integrated transcriptional and metabolomics analysis reveals that Yap transcribes Myc and cooperates with Myc to maintain global transcription of metabolic genes. Yap loss triggers acute metabolic stress, which causes tumor regression while inducing epigenetic reprogramming and Sox2 upregulation in a subset of pancreatic neoplastic cells. Sox2 restores Myc expression and metabolic homeostasis in Yap-deficient neoplastic ductal cells, which gradually re-differentiate into acinar-like cells, partially restoring pancreatic parenchyma in vivo. Both the short-term and long-term effects of Yap loss in inducing cell death and re-differentiation, respectively, are blunted in advanced, poorly differentiated p53-mutant pancreatic tumors. Collectively, these findings reveal a highly dynamic and interdependent metabolic, transcriptional, and epigenetic regulatory network governed by Yap, Myc, Sox2, and p53 that dictates pancreatic tumor metabolism, growth, survival, and differentiation.