Affiliation:
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
Abstract
AbstractTumor‐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.
Funder
National Natural Science Foundation of China
Harbin Medical University Cancer Hospital