Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop

Abstract 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 downstrea...

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Autores principales:	Yan Ding, Guiping Wang, Meixiao Zhan, Xiaohan Sun, Yanran Deng, Yunhe Zhao, Bin Liu, Qingxin Liu, Shian Wu, Zizhang Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/9549fca3d5f74864b8029b48f1e17014
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spelling	oai:doaj.org-article:9549fca3d5f74864b8029b48f1e170142021-12-05T12:04:22ZHippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop10.1038/s41419-021-04423-y2041-4889https://doaj.org/article/9549fca3d5f74864b8029b48f1e170142021-12-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04423-yhttps://doaj.org/toc/2041-4889Abstract 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.Yan DingGuiping WangMeixiao ZhanXiaohan SunYanran DengYunhe ZhaoBin LiuQingxin LiuShian WuZizhang ZhouNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Yan Ding Guiping Wang Meixiao Zhan Xiaohan Sun Yanran Deng Yunhe Zhao Bin Liu Qingxin Liu Shian Wu Zizhang Zhou Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop
description	Abstract 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	article
author	Yan Ding Guiping Wang Meixiao Zhan Xiaohan Sun Yanran Deng Yunhe Zhao Bin Liu Qingxin Liu Shian Wu Zizhang Zhou
author_facet	Yan Ding Guiping Wang Meixiao Zhan Xiaohan Sun Yanran Deng Yunhe Zhao Bin Liu Qingxin Liu Shian Wu Zizhang Zhou
author_sort	Yan Ding
title	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_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_sort	hippo signaling suppresses tumor cell metastasis via a yki-src42a positive feedback loop
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/9549fca3d5f74864b8029b48f1e17014
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Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop

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