IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v562y2018i7725d10.1038_s41586-018-0519-y.html
   My bibliography  Save this article

Necroptosis microenvironment directs lineage commitment in liver cancer

Author

Listed:
  • Marco Seehawer

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Florian Heinzmann

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Luana D’Artista

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Jule Harbig

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Pierre-François Roux

    (Institut Pasteur, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection
    INSERM
    Equipe Labellisée Fondation ARC pour la recherche sur le cancer)

  • Lisa Hoenicke

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Hien Dang

    (Center for Cancer Research, National Cancer Institute)

  • Sabrina Klotz

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Lucas Robinson

    (Institut Pasteur, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection
    INSERM
    Equipe Labellisée Fondation ARC pour la recherche sur le cancer)

  • Grégory Doré

    (Institut Pasteur, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection
    INSERM
    Equipe Labellisée Fondation ARC pour la recherche sur le cancer)

  • Nir Rozenblum

    (Institut Pasteur, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection)

  • Tae-Won Kang

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Rishabh Chawla

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen)

  • Thorsten Buch

    (Institute of Laboratory Animal Science University of Zurich, University of Zurich)

  • Mihael Vucur

    (RWTH University Hospital Aachen, Department of Gastroenterology, Digestive Diseases and Intensive Care Medicine (Department of Medicine III))

  • Mareike Roth

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC))

  • Johannes Zuber

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC))

  • Tom Luedde

    (RWTH University Hospital Aachen, Department of Gastroenterology, Digestive Diseases and Intensive Care Medicine (Department of Medicine III))

  • Bence Sipos

    (University of Tuebingen)

  • Thomas Longerich

    (University Hospital Heidelberg)

  • Mathias Heikenwälder

    (German Cancer Research Center (DKFZ))

  • Xin Wei Wang

    (Center for Cancer Research, National Cancer Institute)

  • Oliver Bischof

    (Institut Pasteur, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection
    INSERM
    Equipe Labellisée Fondation ARC pour la recherche sur le cancer)

  • Lars Zender

    (University Hospital Tuebingen
    Institute of Physiology, Eberhard Karls University Tuebingen
    German Cancer Research Center (DKFZ))

Abstract

Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans. Together, our results provide insight into lineage commitment in liver tumorigenesis, and explain molecularly why common liver-damaging risk factors can lead to either HCC or ICC.

Suggested Citation

  • Marco Seehawer & Florian Heinzmann & Luana D’Artista & Jule Harbig & Pierre-François Roux & Lisa Hoenicke & Hien Dang & Sabrina Klotz & Lucas Robinson & Grégory Doré & Nir Rozenblum & Tae-Won Kang & R, 2018. "Necroptosis microenvironment directs lineage commitment in liver cancer," Nature, Nature, vol. 562(7725), pages 69-75, October.
    • Handle: RePEc:nat:nature:v:562:y:2018:i:7725:d:10.1038_s41586-018-0519-y
    DOI: 10.1038/s41586-018-0519-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0519-y
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-018-0519-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Panpan Tian & Wenwen Yang & Xiaowei Guo & Tixiao Wang & Siyu Tan & Renhui Sun & Rong Xiao & Yuzhen Wang & Deyan Jiao & Yachen Xu & Yanfei Wei & Zhuanchang Wu & Chunyang Li & Lifen Gao & Chunhong Ma & , 2023. "Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:562:y:2018:i:7725:d:10.1038_s41586-018-0519-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.