Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration

Fuqin Fan; Zhixiang He; Lu-Lu Kong; Qinghua Chen; Quan Yuan; Shihao Zhang; Jinjin Ye; Hao Liu; Xiufeng Sun; Jing Geng; Lunzhi Yuan; Lixin Hong; Chen Xiao; Weiji Zhang; Xihuan Sun; Yunzhan Li; Ping Wang; Lihong Huang; Xinrui Wu; Zhiliang Ji; Qiao Wu; Ning-Shao Xia; Nathanael S. Gray; Lanfen Chen; Cai-Hong Yun; Xianming Deng; Dawang Zhou

doi:10.1126/scitranslmed.aaf2304

Research ArticleRegenerative Medicine

Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration

Fuqin Fan¹,²,*,
Zhixiang He¹,²,*,
Lu-Lu Kong³,*,
Qinghua Chen¹,²,*,
Quan Yuan⁴,*,
Shihao Zhang¹,²,
Jinjin Ye¹,²,
Hao Liu¹,²,
Xiufeng Sun¹,²,
Jing Geng¹,²,
Lunzhi Yuan⁴,
Lixin Hong¹,²,
Chen Xiao¹,²,
Weiji Zhang¹,²,
Xihuan Sun¹,²,
Yunzhan Li¹,²,
Ping Wang¹,²,
Lihong Huang¹,²,
Xinrui Wu¹,²,
Zhiliang Ji¹,²,
Qiao Wu¹,²,
Ning-Shao Xia⁴,
Nathanael S. Gray⁵,
Lanfen Chen¹,²,
Cai-Hong Yun³,†,
Xianming Deng¹,²,† and
Dawang Zhou¹,²,†

¹State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
²State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.
³Institute of Systems Biomedicine, Department of Biophysics, and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁴State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, and School of Public Health, Xiamen University, Xiamen, Fujian 361102, China.
⁵Department of Biological Chemistry and Molecular Pharmacology, and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Longwood Center 2207, 360 Longwood Avenue, Boston, MA 02215, USA.

↵†Corresponding author. Email: dwzhou{at}xmu.edu.cn (D.Z.); xmdeng{at}xmu.edu.cn (X.D.); yunch{at}hsc.pku.edu.cn (C.-H.Y.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 17 Aug 2016:
Vol. 8, Issue 352, pp. 352ra108
DOI: 10.1126/scitranslmed.aaf2304

Fuqin Fan

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Zhixiang He

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Lu-Lu Kong

3Institute of Systems Biomedicine, Department of Biophysics, and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.

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Qinghua Chen

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Quan Yuan

4State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, and School of Public Health, Xiamen University, Xiamen, Fujian 361102, China.

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Shihao Zhang

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Jinjin Ye

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Hao Liu

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Xiufeng Sun

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Jing Geng

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Lunzhi Yuan

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Lixin Hong

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Chen Xiao

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Weiji Zhang

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Xihuan Sun

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Yunzhan Li

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Ping Wang

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Lihong Huang

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Xinrui Wu

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Zhiliang Ji

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Qiao Wu

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Ning-Shao Xia

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Nathanael S. Gray

5Department of Biological Chemistry and Molecular Pharmacology, and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Longwood Center 2207, 360 Longwood Avenue, Boston, MA 02215, USA.

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Lanfen Chen

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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Cai-Hong Yun

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For correspondence: dwzhou@xmu.edu.cn xmdeng@xmu.edu.cn yunch@hsc.pku.edu.cn

Xianming Deng

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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For correspondence: dwzhou@xmu.edu.cn xmdeng@xmu.edu.cn yunch@hsc.pku.edu.cn

Dawang Zhou

1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

2State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China.

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For correspondence: dwzhou@xmu.edu.cn xmdeng@xmu.edu.cn yunch@hsc.pku.edu.cn

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Manipulation of the Hippo signaling pathway with a reversible and selective small-molecule inhibitor of Hippo kinase MST1/2 provides a therapeutic option for tissue injury and repair.

Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration

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