Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer

Abstract In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal canc...

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Autores principales:	Wunan Mi, Chuyue Wang, Guang Luo, Jiehan Li, Yizheng Zhang, Meimei Jiang, Chuchu Zhang, Nannan Liu, Xinxiu Jiang, Ge Yang, Lingling Zhang, Ge Zhang, Yingjie Zhang, Yang Fu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3cfc88cc58bf4b919462019446ba917f
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spelling	oai:doaj.org-article:3cfc88cc58bf4b919462019446ba917f2021-12-05T12:08:27ZTargeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer10.1038/s41420-021-00677-92058-7716https://doaj.org/article/3cfc88cc58bf4b919462019446ba917f2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00677-9https://doaj.org/toc/2058-7716Abstract In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo. Studies have confirmed that higher concentrations of ROS leads to autophagy or cell death. In this research, the role of CC90003-induced ROS was verified. But after inhibiting ROS by two kinds of ROS inhibitors NAC and SFN, the autophagy induced by CC90003 decreased, while cell death strengthened. In parallel, protective autophagy was also induced, while in a p53-dependent manner. After silencing p53 or using the p53 inhibitor PFTα, the autophagy induced by CC90003 was weakened and the rate of cell death increases. Therefore, we confirmed that CC90003 could induce autophagy by activating ROS/p53. Furthermore, in the xenograft mouse model, the effect was obtained remarkably in the combinational treatment group of CC90003 plus CQ, comparing with that of the single treatment groups. In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for clinical therapy.Wunan MiChuyue WangGuang LuoJiehan LiYizheng ZhangMeimei JiangChuchu ZhangNannan LiuXinxiu JiangGe YangLingling ZhangGe ZhangYingjie ZhangYang FuNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Wunan Mi Chuyue Wang Guang Luo Jiehan Li Yizheng Zhang Meimei Jiang Chuchu Zhang Nannan Liu Xinxiu Jiang Ge Yang Lingling Zhang Ge Zhang Yingjie Zhang Yang Fu Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
description	Abstract In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo. Studies have confirmed that higher concentrations of ROS leads to autophagy or cell death. In this research, the role of CC90003-induced ROS was verified. But after inhibiting ROS by two kinds of ROS inhibitors NAC and SFN, the autophagy induced by CC90003 decreased, while cell death strengthened. In parallel, protective autophagy was also induced, while in a p53-dependent manner. After silencing p53 or using the p53 inhibitor PFTα, the autophagy induced by CC90003 was weakened and the rate of cell death increases. Therefore, we confirmed that CC90003 could induce autophagy by activating ROS/p53. Furthermore, in the xenograft mouse model, the effect was obtained remarkably in the combinational treatment group of CC90003 plus CQ, comparing with that of the single treatment groups. In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for clinical therapy.
format	article
author	Wunan Mi Chuyue Wang Guang Luo Jiehan Li Yizheng Zhang Meimei Jiang Chuchu Zhang Nannan Liu Xinxiu Jiang Ge Yang Lingling Zhang Ge Zhang Yingjie Zhang Yang Fu
author_facet	Wunan Mi Chuyue Wang Guang Luo Jiehan Li Yizheng Zhang Meimei Jiang Chuchu Zhang Nannan Liu Xinxiu Jiang Ge Yang Lingling Zhang Ge Zhang Yingjie Zhang Yang Fu
author_sort	Wunan Mi
title	Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
title_short	Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
title_full	Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
title_fullStr	Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
title_full_unstemmed	Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer
title_sort	targeting erk induced cell death and p53/ros-dependent protective autophagy in colorectal cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/3cfc88cc58bf4b919462019446ba917f
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Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer

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