Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma

Abstract Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreove...

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Main Authors: Fang Zhen, Yue Sun, Hongyi Wang, Wei Liu, Xiao Liang, Yaru Wang, Qi Wang, Jing Hu
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202405731
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author Fang Zhen
Yue Sun
Hongyi Wang
Wei Liu
Xiao Liang
Yaru Wang
Qi Wang
Jing Hu
author_facet Fang Zhen
Yue Sun
Hongyi Wang
Wei Liu
Xiao Liang
Yaru Wang
Qi Wang
Jing Hu
author_sort Fang Zhen
collection DOAJ
description Abstract Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell‐derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell‐derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.
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issn 2198-3844
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publisher Wiley
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spelling doaj-art-cb37fa90ab534d4bbe64599f021eb9f02025-08-20T02:17:09ZengWileyAdvanced Science2198-38442024-10-011138n/an/a10.1002/advs.202405731Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung AdenocarcinomaFang Zhen0Yue Sun1Hongyi Wang2Wei Liu3Xiao Liang4Yaru Wang5Qi Wang6Jing Hu7Department of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaDepartment of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaDepartment of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaDepartment of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaKey laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University) Ministry of Education Harbin Heilongjiang 150081 ChinaDepartment of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaDepartment of Medicinal Chemistry and Natural Medicinal Chemistry College of Pharmacy Harbin Medical University No. 157 Baojian Road Harbin Heilongjiang 150081 ChinaDepartment of Breast Medical Oncology Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping Road Harbin Heilongjiang 150040 ChinaAbstract Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell‐derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell‐derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.https://doi.org/10.1002/advs.202405731extracellular vesiclesinvadopodialung adenocarcinomatumor cell metastasisubiquitin‐specific protease 22
spellingShingle Fang Zhen
Yue Sun
Hongyi Wang
Wei Liu
Xiao Liang
Yaru Wang
Qi Wang
Jing Hu
Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
Advanced Science
extracellular vesicles
invadopodia
lung adenocarcinoma
tumor cell metastasis
ubiquitin‐specific protease 22
title Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
title_full Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
title_fullStr Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
title_full_unstemmed Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
title_short Ubiquitin‐Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma
title_sort ubiquitin specific protease 22 plays a key role in increasing extracellular vesicle secretion and regulating cell motility of lung adenocarcinoma
topic extracellular vesicles
invadopodia
lung adenocarcinoma
tumor cell metastasis
ubiquitin‐specific protease 22
url https://doi.org/10.1002/advs.202405731
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