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Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop
Metastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts pro...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642408/ https://www.ncbi.nlm.nih.gov/pubmed/34862372 http://dx.doi.org/10.1038/s41419-021-04423-y |
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author | Ding, Yan Wang, Guiping Zhan, Meixiao Sun, Xiaohan Deng, Yanran Zhao, Yunhe Liu, Bin Liu, Qingxin Wu, Shian Zhou, Zizhang |
author_facet | Ding, Yan Wang, Guiping Zhan, Meixiao Sun, Xiaohan Deng, Yanran Zhao, Yunhe Liu, Bin Liu, Qingxin Wu, Shian Zhou, Zizhang |
author_sort | Ding, Yan |
collection | PubMed |
description | Metastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts promotes tumor cell migration in a Yki-dependent manner. Furthermore, we identify that inhibition of the Hippo pathway promotes tumor cell migration through transcriptional activating src42A, a Drosophila homolog of the SRC oncogene. Yki activates src42A transcription through direct binding its intron region. Intriguingly, Src42A further increases Yki transcriptional activity to form a positive feedback loop. Finally, we show that SRC is also a target of YAP and important for YAP to promote the migration of human hepatocellular carcinoma cells. Together, our findings uncover a conserved Yki/YAP-Src42A/SRC positive feedback loop promoting tumor cell migration and provide SRC as a potential therapeutic target for YAP-driven metastatic tumors. |
format | Online Article Text |
id | pubmed-8642408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86424082021-12-15 Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop Ding, Yan Wang, Guiping Zhan, Meixiao Sun, Xiaohan Deng, Yanran Zhao, Yunhe Liu, Bin Liu, Qingxin Wu, Shian Zhou, Zizhang Cell Death Dis Article Metastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts promotes tumor cell migration in a Yki-dependent manner. Furthermore, we identify that inhibition of the Hippo pathway promotes tumor cell migration through transcriptional activating src42A, a Drosophila homolog of the SRC oncogene. Yki activates src42A transcription through direct binding its intron region. Intriguingly, Src42A further increases Yki transcriptional activity to form a positive feedback loop. Finally, we show that SRC is also a target of YAP and important for YAP to promote the migration of human hepatocellular carcinoma cells. Together, our findings uncover a conserved Yki/YAP-Src42A/SRC positive feedback loop promoting tumor cell migration and provide SRC as a potential therapeutic target for YAP-driven metastatic tumors. Nature Publishing Group UK 2021-12-03 /pmc/articles/PMC8642408/ /pubmed/34862372 http://dx.doi.org/10.1038/s41419-021-04423-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ding, Yan Wang, Guiping Zhan, Meixiao Sun, Xiaohan Deng, Yanran Zhao, Yunhe Liu, Bin Liu, Qingxin Wu, Shian Zhou, Zizhang Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title | Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title_full | Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title_fullStr | Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title_full_unstemmed | Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title_short | Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop |
title_sort | hippo signaling suppresses tumor cell metastasis via a yki-src42a positive feedback loop |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642408/ https://www.ncbi.nlm.nih.gov/pubmed/34862372 http://dx.doi.org/10.1038/s41419-021-04423-y |
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