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Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer

Author

Listed:
  • Supriya K. Saha

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Christine A. Parachoniak

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Krishna S. Ghanta

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Julien Fitamant

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Kenneth N. Ross

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Mortada S. Najem

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Sushma Gurumurthy

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Esra A. Akbay

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Daniela Sia

    (HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Catalonia 08036, Spain
    Mount Sinai Liver Cancer Program, Dept of Medicine. Icahn School of Medicine at Mount Sinai
    Gastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute)

  • Helena Cornella

    (HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Catalonia 08036, Spain)

  • Oriana Miltiadous

    (Mount Sinai Liver Cancer Program, Dept of Medicine. Icahn School of Medicine at Mount Sinai)

  • Chad Walesky

    (Toxicology and Therapeutics, University of Kansas Medical Center)

  • Vikram Deshpande

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Andrew X. Zhu

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Aram F. Hezel

    (University of Rochester Medical Center)

  • Katharine E. Yen

    (Agios Pharmaceuticals)

  • Kimberly S. Straley

    (Agios Pharmaceuticals)

  • Jeremy Travins

    (Agios Pharmaceuticals)

  • Janeta Popovici-Muller

    (Agios Pharmaceuticals)

  • Camelia Gliser

    (Agios Pharmaceuticals)

  • Cristina R. Ferrone

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Udayan Apte

    (Toxicology and Therapeutics, University of Kansas Medical Center)

  • Josep M. Llovet

    (HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Catalonia 08036, Spain
    Mount Sinai Liver Cancer Program, Dept of Medicine. Icahn School of Medicine at Mount Sinai
    Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia 08010, Spain
    University of Barcelona, Catalonia 08036, Spain)

  • Kwok-Kin Wong

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Sridhar Ramaswamy

    (Massachusetts General Hospital Cancer Center, Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Nabeel Bardeesy

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

Abstract

Gain-of-function mutations in isocitrate dehydrogenase (IDH) are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly cancer of the liver bile ducts; now mutant IDH is shown to block liver cell differentiation through the suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence, leading to expansion of liver progenitor cells primed for progression to IHCC.

Suggested Citation

  • Supriya K. Saha & Christine A. Parachoniak & Krishna S. Ghanta & Julien Fitamant & Kenneth N. Ross & Mortada S. Najem & Sushma Gurumurthy & Esra A. Akbay & Daniela Sia & Helena Cornella & Oriana Milti, 2014. "Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer," Nature, Nature, vol. 513(7516), pages 110-114, September.
    • Handle: RePEc:nat:nature:v:513:y:2014:i:7516:d:10.1038_nature13441
    DOI: 10.1038/nature13441
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    Cited by:

    1. Dan Xiao & Wen Zhang & Xiaoting Guo & Yidong Liu & Chunxia Hu & Shiting Guo & Zhaoqi Kang & Xianzhi Xu & Cuiqing Ma & Chao Gao & Ping Xu, 2021. "A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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