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

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 Miltiadous, Chad Walesky, Vikram Deshpande, Andrew X. Zhu, Aram F. Hezel, Katharine E. Yen, Kimberly S. Straley, Jeremy Travins, Janeta Popovici-Muller, Camelia Gliser, Cristina R. Ferrone, Udayan Apte, Josep M. Llovet, Kwok-Kin Wong, Sridhar Ramaswamy and Nabeel Bardeesy ()
Additional contact information
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
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
Kwok-Kin Wong: Dana-Farber Cancer Institute, Harvard Medical School
Sridhar Ramaswamy: Massachusetts General Hospital Cancer Center, Harvard Medical School
Nabeel Bardeesy: Massachusetts General Hospital Cancer Center, Harvard Medical School

Nature, 2014, vol. 513, issue 7516, 110-114

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.

Date: 2014
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DOI: 10.1038/nature13441

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