UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma

Abstract Ubiquitination displays a crucial role in various biological functions, such as protein degradation, signal transduction, and cellular homeostasis. Accumulating evidence has indicated that ubiquitination is essential in cancer progression. Ubiquitin-conjugating enzyme E2S (UBE2S) is a membe...

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Autores principales:	Liang Gui, Sicai Zhang, Yongzi Xu, Hongwei Zhang, Ying Zhu, Lianbao Kong
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/654dae1d73c84d1c9fc747958853203a
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spelling	oai:doaj.org-article:654dae1d73c84d1c9fc747958853203a2021-11-21T12:08:47ZUBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma10.1038/s41420-021-00750-32058-7716https://doaj.org/article/654dae1d73c84d1c9fc747958853203a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00750-3https://doaj.org/toc/2058-7716Abstract Ubiquitination displays a crucial role in various biological functions, such as protein degradation, signal transduction, and cellular homeostasis. Accumulating evidence has indicated that ubiquitination is essential in cancer progression. Ubiquitin-conjugating enzyme E2S (UBE2S) is a member of ubiquitin-conjugating enzyme family of the ubiquitin system and its role in hepatocellular cancer (HCC) is largely unknown. We investigated the role of UBE2S in HCC and found UBE2S upregulation is relevant with large tumor size, recurrence, and advanced TNM stage, serving as an independent risk factor of overall survival (OS) and disease-free survival (DFS) for HCC patients. We conducted in vitro experiments and found that in HCC cells, UBE2S overexpression increases the resistance to 5-FU and oxaliplatin, while UBE2S knockdown achieves an opposite effect. UBE2S is transcriptionally activated by the binding of FOXM1 to UBE2S promoter, which induces its upregulation and reduces PTEN protein level by promoting PTEN ubiquitination at Lys60 and Lys327 and facilitating AKT phosphorylation. The promotional effect of FOXM1-UBE2S axis on HCC cell chemoresistance is attenuated by allosteric AKT inhibitor, MK2206. In conclusion, our results reveal that UBE2S is a prognostic biomarker for HCC patients, and the FOXM1-UBE2S-PTEN-p-AKT signaling axis might be a promising target for the treatment of HCC.Liang GuiSicai ZhangYongzi XuHongwei ZhangYing ZhuLianbao KongNature 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 Liang Gui Sicai Zhang Yongzi Xu Hongwei Zhang Ying Zhu Lianbao Kong UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
description	Abstract Ubiquitination displays a crucial role in various biological functions, such as protein degradation, signal transduction, and cellular homeostasis. Accumulating evidence has indicated that ubiquitination is essential in cancer progression. Ubiquitin-conjugating enzyme E2S (UBE2S) is a member of ubiquitin-conjugating enzyme family of the ubiquitin system and its role in hepatocellular cancer (HCC) is largely unknown. We investigated the role of UBE2S in HCC and found UBE2S upregulation is relevant with large tumor size, recurrence, and advanced TNM stage, serving as an independent risk factor of overall survival (OS) and disease-free survival (DFS) for HCC patients. We conducted in vitro experiments and found that in HCC cells, UBE2S overexpression increases the resistance to 5-FU and oxaliplatin, while UBE2S knockdown achieves an opposite effect. UBE2S is transcriptionally activated by the binding of FOXM1 to UBE2S promoter, which induces its upregulation and reduces PTEN protein level by promoting PTEN ubiquitination at Lys60 and Lys327 and facilitating AKT phosphorylation. The promotional effect of FOXM1-UBE2S axis on HCC cell chemoresistance is attenuated by allosteric AKT inhibitor, MK2206. In conclusion, our results reveal that UBE2S is a prognostic biomarker for HCC patients, and the FOXM1-UBE2S-PTEN-p-AKT signaling axis might be a promising target for the treatment of HCC.
format	article
author	Liang Gui Sicai Zhang Yongzi Xu Hongwei Zhang Ying Zhu Lianbao Kong
author_facet	Liang Gui Sicai Zhang Yongzi Xu Hongwei Zhang Ying Zhu Lianbao Kong
author_sort	Liang Gui
title	UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
title_short	UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
title_full	UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
title_fullStr	UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
title_full_unstemmed	UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma
title_sort	ube2s promotes cell chemoresistance through pten-akt signaling in hepatocellular carcinoma
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/654dae1d73c84d1c9fc747958853203a
work_keys_str_mv	AT lianggui ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma AT sicaizhang ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma AT yongzixu ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma AT hongweizhang ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma AT yingzhu ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma AT lianbaokong ube2spromotescellchemoresistancethroughptenaktsignalinginhepatocellularcarcinoma
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UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma

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