2. Academic Validation
  3. Ubiquitin-Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma

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

  • Adv Sci (Weinh). 2024 Aug 5:e2405731. doi: 10.1002/advs.202405731.
Fang Zhen 1,  Yue Sun 1,  Hongyi Wang 1,  Wei Liu 1,  Xiao Liang 2,  Yaru Wang 1,  Qi Wang 3,  Jing Hu 1 2
Affiliations

Affiliations

  • 1 Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, No. 150 Haping Road, Harbin, Heilongjiang, 150040, China.
  • 2 Key laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, 150081, China.
  • 3 Department of Medicinal Chemistry and Natural Medicinal Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Harbin, Heilongjiang, 150081, China.
PMID: 39101247 DOI: 10.1002/advs.202405731
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.

Keywords

extracellular vesicles; invadopodia; lung adenocarcinoma; tumor cell metastasis; ubiquitin‐specific protease 22.

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