The Janus kinase 1 is critical for pancreatic cancer initiation and progression.

Autor:	Shrestha H; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA., Rädler PD; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Dennaoui R; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA., Wicker MN; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA., Rajbhandari N; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Sun Y; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Peck AR; Department of Pharmacology, Physiology & Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA., Vistisen K; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA., Triplett AA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Beydoun R; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA; Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Sterneck E; Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Saur D; Division of Translational Cancer Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Translational Cancer Research and Institute of Experimental Cancer Therapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany., Rui H; Department of Pharmacology, Physiology & Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA., Wagner KU; Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA. Electronic address: kuwagner@wayne.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114202. Date of Electronic Publication: 2024 May 10.
DOI:	10.1016/j.celrep.2024.114202
Abstrakt:	Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRAS G12D -induced pancreatic tumors, and we establish that JAK1 is essential for the constitutive activation of STAT3, whose activation is a prominent characteristic of PDAC. We identify CCAAT/enhancer binding protein δ (C/EBPδ) as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPδ was sufficient to restore the growth of JAK1-deficient cancer cells as tumorspheres and in xenografted mice. Collectively, the findings of this study suggest that JAK1 executes important functions of inflammatory cytokines through C/EBPδ and may serve as a molecular target for PDAC prevention and treatment. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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