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C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling

Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transc...

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Autores principales: Zhu, Pingping, Wang, Yanying, Du, Ying, He, Lei, Huang, Guanling, Zhang, Geng, Yan, Xinlong, Fan, Zusen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479000/
https://www.ncbi.nlm.nih.gov/pubmed/25985737
http://dx.doi.org/10.1038/ncomms8122
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author Zhu, Pingping
Wang, Yanying
Du, Ying
He, Lei
Huang, Guanling
Zhang, Geng
Yan, Xinlong
Fan, Zusen
author_facet Zhu, Pingping
Wang, Yanying
Du, Ying
He, Lei
Huang, Guanling
Zhang, Geng
Yan, Xinlong
Fan, Zusen
author_sort Zhu, Pingping
collection PubMed
description Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transcriptome datasets and our experimental data, we find that C8orf4 is weakly expressed in HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver CSCs and tumour propagation. We show that NOTCH2 is activated in liver CSCs. C8orf4 is located in the cytoplasm of HCC tumour cells and associates with the NOTCH2 intracellular domain, which impedes the nuclear translocation of N2ICD. C8orf4 deletion causes the nuclear translocation of N2ICD that triggers the NOTCH2 signalling, which sustains the stemness of liver CSCs. Finally, NOTCH2 activation levels are consistent with clinical severity and prognosis of HCC patients. Altogether, C8orf4 negatively regulates the self-renewal of liver CSCs via suppression of NOTCH2 signalling.
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spelling pubmed-44790002015-06-29 C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling Zhu, Pingping Wang, Yanying Du, Ying He, Lei Huang, Guanling Zhang, Geng Yan, Xinlong Fan, Zusen Nat Commun Article Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transcriptome datasets and our experimental data, we find that C8orf4 is weakly expressed in HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver CSCs and tumour propagation. We show that NOTCH2 is activated in liver CSCs. C8orf4 is located in the cytoplasm of HCC tumour cells and associates with the NOTCH2 intracellular domain, which impedes the nuclear translocation of N2ICD. C8orf4 deletion causes the nuclear translocation of N2ICD that triggers the NOTCH2 signalling, which sustains the stemness of liver CSCs. Finally, NOTCH2 activation levels are consistent with clinical severity and prognosis of HCC patients. Altogether, C8orf4 negatively regulates the self-renewal of liver CSCs via suppression of NOTCH2 signalling. Nature Pub. Group 2015-05-19 /pmc/articles/PMC4479000/ /pubmed/25985737 http://dx.doi.org/10.1038/ncomms8122 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhu, Pingping
Wang, Yanying
Du, Ying
He, Lei
Huang, Guanling
Zhang, Geng
Yan, Xinlong
Fan, Zusen
C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title_full C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title_fullStr C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title_full_unstemmed C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title_short C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
title_sort c8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of notch2 signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479000/
https://www.ncbi.nlm.nih.gov/pubmed/25985737
http://dx.doi.org/10.1038/ncomms8122
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