<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.</p>
</abstract>

Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.

Fingolimod exerts <italic>in vitro</italic> anticancer activity against hepatocellular carcinoma cell lines <italic>via</italic> YAP/TAZ suppression

Zhejiang Province Key Laboratory of Anticancer Drug Research

College of Pharmaceutical Sciences, Zhejiang University

Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province

Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine

Department of Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province

Affiliated Hangzhou First People´s Hospital, Zhejiang University School of Medicine

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery

The Second Affiliated Hospital, School of Medicine Zhejiang University

The Westlake Laboratory of Life Sciences and Biomedicine

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fingolimod exerts  anticancer activity against hepatocellular carcinoma cell lines  YAP/TAZ suppression

Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling...

Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression

Published Online: Apr 13, 2022

Page range: 427 - 436

Accepted: Jan 19, 2022

DOI: https://doi.org/10.2478/acph-2022-0029

Keywords
fingolimod, hepatocellular carcinoma, hippo signalling, YAP/TAZ

© 2022 Jiamin Du et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression

Published Online: Apr 13, 2022

Page range: 427 - 436

Accepted: Jan 19, 2022

DOI: https://doi.org/10.2478/acph-2022-0029

Keywordsfingolimod, hepatocellular carcinoma, hippo signalling, YAP/TAZ

© 2022 Jiamin Du et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
fingolimod, hepatocellular carcinoma, hippo signalling, YAP/TAZ