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Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans.

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收录情况： ◇ SCIE

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机构： [1]Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA [3]Second Clinical Medical School, Beijing University of Chinese Medicine, Beijing, China [4]Liver Transplantation Division, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China [5]Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing, China [6]Department of Pediatrics and Institute for Computational Health Sciences, University of California, San Francisco, CA, USA [7]National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy [8]Institute of Pathology, University of Greifswald, Greifswald, Germany [9]The Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

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Primary liver cancer consists mainly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A subset of human HCCs expresses a ICC-like gene signature and is classified as ICC-like HCC. The Hippo pathway is a critical regulator of normal and malignant liver development. However, the precise function(s) of the Hippo cascade along liver carcinogenesis remain to be fully delineated. The role of the Hippo pathway in a murine mixed HCC/ICC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated. The authors demonstrated the inactivation of Hippo in AKT/Ras liver tumors leading to nuclear localization of Yap and TAZ. Coexpression of AKT/Ras with Lats2, which activates Hippo, or the dominant negative form of TEAD2 (dnTEAD2), which blocks Yap/TAZ activity, resulted in delayed hepatocarcinogenesis and elimination of ICC-like lesions in the liver. Mechanistically, Notch2 expression was found to be down-regulated by the Hippo pathway in liver tumors. Overexpression of Lats2 or dnTEAD2 in human HCC cell lines inhibited their growth and led to the decreased expression of ICC-like markers, as well as Notch2 expression. Altogether, this study supports the key role of the Hippo cascade in regulating the differentiation status of liver tumors. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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出版当年[2018]版：

大类 | 2 区

医学

小类 | 2 区病理学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区病理学

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出版当年[2018]版：

Q1 PATHOLOGY

最新[2023]版：

Q1 PATHOLOGY

影响因子： 4.7 最新[2023版] 4.8 最新五年平均 3.762 出版当年[2018版] 4.364 出版当年五年平均 4.069 出版前一年[2017版] 3.491 出版后一年[2019版]

第一作者：

第一作者机构： [1]Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA [9]The Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

通讯作者：

通讯机构： [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA [8]Institute of Pathology, University of Greifswald, Greifswald, Germany [*1]Institut für Pathologie, Universitätsmedizin Greifswald, Friedrich-LoefflerStrasse 23e, 17489 Greifswald, Germany [*2]UCSF, 513 Parnassus Avenue, San Francisco, CA 94143, U.S.A

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