AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA

Metastasis is considered the leading cause of cancer death due to the limited possibilities to therapeutically target this process. How the ubiquitination machinery contributes to metastasis remains underexplored. Angio-associated migratory cell protein (AAMP), a ubiquitously expressed protein invol...

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Autores principales:	Yuhui Wu, Bofang Liu, Weiqiang Lin, Rongjie Zhao, Weidong Han, Jiansheng Xie
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	AAMP colorectal cancer metastasis RhoA SMURF2 ubiquitination Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bf1f2c41243e4b9aaa1f98caaa642c12
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spelling	oai:doaj.org-article:bf1f2c41243e4b9aaa1f98caaa642c122021-11-28T04:34:41ZAAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA2372-770510.1016/j.omto.2021.11.007https://doaj.org/article/bf1f2c41243e4b9aaa1f98caaa642c122021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S237277052100156Xhttps://doaj.org/toc/2372-7705Metastasis is considered the leading cause of cancer death due to the limited possibilities to therapeutically target this process. How the ubiquitination machinery contributes to metastasis remains underexplored. Angio-associated migratory cell protein (AAMP), a ubiquitously expressed protein involved in cell migration, has been reported to play oncogenic roles in breast and non-small cell lung cancer (NSCLC). However, the role of AAMP in colorectal cancer (CRC) has not been demonstrated. Here, we report that AAMP is aberrantly upregulated in metastatic CRC and that AAMP upregulation is correlated with the poor survival of CRC patients. AAMP knockdown significantly attenuated the migration and invasion of CRC cells, while AAMP overexpression led to the opposite effects. Mechanistically, we identified Ras homolog family member A (RhoA) as a target of AAMP. Smad ubiquitin regulatory factor (SMURF) 2 was previously found to be a CRC suppressor. Notably, we discovered here that SMURF2 acted as an E3 ubiquitin ligase to mediate the ubiquitination and degradation of RhoA. AAMP stabilized RhoA by binding to it and suppressing its SMURF2-mediated ubiquitination and degradation. Subsequently, the level of active RhoA was increased, thereby accelerating CRC cell migration and invasion. These findings indicate a new potential antitumor target for CRC.Yuhui WuBofang LiuWeiqiang LinRongjie ZhaoWeidong HanJiansheng XieElsevierarticleAAMPcolorectal cancermetastasisRhoASMURF2ubiquitinationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 515-530 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AAMP colorectal cancer metastasis RhoA SMURF2 ubiquitination Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	AAMP colorectal cancer metastasis RhoA SMURF2 ubiquitination Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yuhui Wu Bofang Liu Weiqiang Lin Rongjie Zhao Weidong Han Jiansheng Xie AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
description	Metastasis is considered the leading cause of cancer death due to the limited possibilities to therapeutically target this process. How the ubiquitination machinery contributes to metastasis remains underexplored. Angio-associated migratory cell protein (AAMP), a ubiquitously expressed protein involved in cell migration, has been reported to play oncogenic roles in breast and non-small cell lung cancer (NSCLC). However, the role of AAMP in colorectal cancer (CRC) has not been demonstrated. Here, we report that AAMP is aberrantly upregulated in metastatic CRC and that AAMP upregulation is correlated with the poor survival of CRC patients. AAMP knockdown significantly attenuated the migration and invasion of CRC cells, while AAMP overexpression led to the opposite effects. Mechanistically, we identified Ras homolog family member A (RhoA) as a target of AAMP. Smad ubiquitin regulatory factor (SMURF) 2 was previously found to be a CRC suppressor. Notably, we discovered here that SMURF2 acted as an E3 ubiquitin ligase to mediate the ubiquitination and degradation of RhoA. AAMP stabilized RhoA by binding to it and suppressing its SMURF2-mediated ubiquitination and degradation. Subsequently, the level of active RhoA was increased, thereby accelerating CRC cell migration and invasion. These findings indicate a new potential antitumor target for CRC.
format	article
author	Yuhui Wu Bofang Liu Weiqiang Lin Rongjie Zhao Weidong Han Jiansheng Xie
author_facet	Yuhui Wu Bofang Liu Weiqiang Lin Rongjie Zhao Weidong Han Jiansheng Xie
author_sort	Yuhui Wu
title	AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
title_short	AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
title_full	AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
title_fullStr	AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
title_full_unstemmed	AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA
title_sort	aamp promotes colorectal cancermetastasis by suppressing smurf2-mediatedubiquitination and degradation of rhoa
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bf1f2c41243e4b9aaa1f98caaa642c12
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AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA

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