SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer

• Published in: Cancer letters Vol. 577; p. 216400
• Main Authors: Liu, Xiao, Li, Rui, Chen, Xiao, Yao, Jie, Wang, Qingxiang, Zhang, Jinghong, Jiang, Yuanyuan, Qu, Yiqing
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 28-11-2023
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2023.216400

Lung cancer is the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Our previous study confirmed that synaptotagmin 7 (SYT7) promoted NSCLC metastasis in vivo and in vitro. Studies have shown that SYT7 is an important regulatory molecule of exocytosis in various cells. However, the characteristics of SYT7 across cancers and the function of SYT7 in tumor exosome secretion remain unclear. In this study, we conducted systematic pancancer analyses of SYT7, namely, analyses of expression patterns, diagnostic and prognostic values, genetic alterations, methylation, immune infiltration, and potential biological pathways. Furthermore, we demonstrated that SYT7 increased the secretion of exosomes from A549 and H1299 cells, promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs). Notably, SYT7 promoted angiogenesis by transferring exosomes containing the molecule centrosomal protein of 55 kDa (CEP55) protein to HUVECs. The CEP55 protein levels was downregulated in STAT1 inhibitor-treating SYT7-overexpresion NSCLC cells. We further found that SYT7 activated the mTOR signaling pathway through the downstream molecule CEP55, thereby promoting the invasion and metastasis of NSCLC cells. SYT7 promoted exosome secretion by NSCLC cells through upregulating syntaxin-1a and syntaxin-3. In vivo, SYT7 promoted the tumorigenesis, angiogenesis and metastasis of A549 cells through the exosome pathway. Our study is of great importance for understanding the mechanism of tumor exosome secretion and the role of exosomes in tumor progression.
•SYT7 is a potential pancancer biomarker.•SYT7 promoted the secretion of exosomes in NSCLC cells.•SYT7 promoted angiogenesis by transferring exosomes containing CEP55 protein to HUVECs.•SYT7 may regulate NSCLC exosome secretion through upregulating STX1A and STX3.