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Two Hippo signaling modules orchestrate liver size and tumorigenesis.
Qi, Sixian; Zhong, Zhenxing; Zhu, Yuwen; Wang, Yebin; Ma, Mingyue; Wang, Yu; Liu, Xincheng; Jin, Ruxin; Jiao, Zhihan; Zhu, Rui; Sha, Zhao; Dang, Kyvan; Liu, Ying; Lim, Dae-Sik; Mao, Junhao; Zhang, Lei; Yu, Fa-Xing.
  • Qi S; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Zhong Z; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhu Y; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Wang Y; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ma M; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Wang Y; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Liu X; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Jin R; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Jiao Z; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Zhu R; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Sha Z; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Dang K; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Liu Y; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Lim DS; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Mao J; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
  • Zhang L; The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Yu FX; Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China.
EMBO J ; 42(11): e112126, 2023 06 01.
Article en En | MEDLINE | ID: mdl-36919851
ABSTRACT
The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Animals Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Animals Idioma: En Año: 2023 Tipo del documento: Article