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Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade

Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC) cell lines an...

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Autores principales: Jia, Jiaoyuan, Qiao, Yu, Pilo, Maria G., Cigliano, Antonio, Liu, Xianqiong, Shao, Zixuan, Calvisi, Diego F., Chen, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587291/
https://www.ncbi.nlm.nih.gov/pubmed/28877210
http://dx.doi.org/10.1371/journal.pone.0184068
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author Jia, Jiaoyuan
Qiao, Yu
Pilo, Maria G.
Cigliano, Antonio
Liu, Xianqiong
Shao, Zixuan
Calvisi, Diego F.
Chen, Xin
author_facet Jia, Jiaoyuan
Qiao, Yu
Pilo, Maria G.
Cigliano, Antonio
Liu, Xianqiong
Shao, Zixuan
Calvisi, Diego F.
Chen, Xin
author_sort Jia, Jiaoyuan
collection PubMed
description Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC) cell lines and the molecular mechanisms involved. For this purpose, we performed cell proliferation assay by colony-forming ability in seven human HCC cells subjected to XAV-939 and G007-LK Tankyrase inhibitors. Noticeably, the two Tankyrase inhibitors suppressed the HCC cell growth in a dose-dependent manner. Furthermore, we found that Tankyrase inhibitors synergized with MEK and AKT inhibitors to suppress HCC cell proliferation. At the molecular level, Tankyrase inhibitors significantly decreased YAP protein levels, reduced the expression of YAP target genes, and inhibited YAP/TEAD luciferase reporter activity. In addition, Tankyrase inhibitors administration was accompanied by upregulation of Angiomotin-like 1 (AMOTL1) and Angiomotin-like 2 (AMOTL2) proteins, two major negative regulators of YAP. Altogether, the present data indicate that XAV-939 and G007-LK Tankyrase inhibitors could suppress proliferation of hepatocellular carcinoma cells and downregulate YAP/TAZ by stabilizing AMOTL1 and AMOTL2 proteins, thus representing new potential anticancer drugs against hepatocellular carcinoma.
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spelling pubmed-55872912017-09-15 Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade Jia, Jiaoyuan Qiao, Yu Pilo, Maria G. Cigliano, Antonio Liu, Xianqiong Shao, Zixuan Calvisi, Diego F. Chen, Xin PLoS One Research Article Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC) cell lines and the molecular mechanisms involved. For this purpose, we performed cell proliferation assay by colony-forming ability in seven human HCC cells subjected to XAV-939 and G007-LK Tankyrase inhibitors. Noticeably, the two Tankyrase inhibitors suppressed the HCC cell growth in a dose-dependent manner. Furthermore, we found that Tankyrase inhibitors synergized with MEK and AKT inhibitors to suppress HCC cell proliferation. At the molecular level, Tankyrase inhibitors significantly decreased YAP protein levels, reduced the expression of YAP target genes, and inhibited YAP/TEAD luciferase reporter activity. In addition, Tankyrase inhibitors administration was accompanied by upregulation of Angiomotin-like 1 (AMOTL1) and Angiomotin-like 2 (AMOTL2) proteins, two major negative regulators of YAP. Altogether, the present data indicate that XAV-939 and G007-LK Tankyrase inhibitors could suppress proliferation of hepatocellular carcinoma cells and downregulate YAP/TAZ by stabilizing AMOTL1 and AMOTL2 proteins, thus representing new potential anticancer drugs against hepatocellular carcinoma. Public Library of Science 2017-09-06 /pmc/articles/PMC5587291/ /pubmed/28877210 http://dx.doi.org/10.1371/journal.pone.0184068 Text en © 2017 Jia et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jia, Jiaoyuan
Qiao, Yu
Pilo, Maria G.
Cigliano, Antonio
Liu, Xianqiong
Shao, Zixuan
Calvisi, Diego F.
Chen, Xin
Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title_full Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title_fullStr Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title_full_unstemmed Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title_short Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
title_sort tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the hippo cascade
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587291/
https://www.ncbi.nlm.nih.gov/pubmed/28877210
http://dx.doi.org/10.1371/journal.pone.0184068
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