Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Gene. 2024 Jan 20;892:147873. doi: 10.1016/j.gene.2023.147873. Epub 2023 Oct 12.
Exosome-mediated epithelial mesenchymal transition (EMT) is key to cancer metastasis. c-Src is involved in the secretion of exosomes and initiation of EMT. Effects of exosomes from metastatic non-small cell lung carcinoma (NSCLC) cells on the EMT process in primary NSCLC cells were assessed. Levels of c-Src in NSCLC tissues were detected and the influence of exosomes from metastatic NSCLC cells on the exosome secretion and EMT process in primary NSCLC cells was assessed. The expression of c-Src was modulated, and the influence on the secretion of exosomes and EMT initiation was evaluated. The level of c-Src was higher in NSCLC specimen and NSCLC cells with promoted EMT process. The suppression of c-Src inhibited secretion of exosomes. Exosomes from metastatic NSCLC cells enhanced migration and invasion abilities of primary NSCLC cells, which had identical effects to c-Src overexpression. The suppression of c-Src inhibited growth and metastasis of solid tumors as well as secretion of exosomes, while the injection of exosomes with c-Src overexpression promoted lung metastasis. TGF-β1 restored the invasion and migration abilities even with c-Src knockdown. The exosomes from metastatic NSCLC cells with high c-Src expression of can increase c-Src level in primary NSCLC cells, contributing to the promoted EMT process through TGF-β1 pathway.
外泌体介导的上皮间质转化（EMT）是癌症转移的关键。c-Src 参与外泌体的分泌和 EMT 的启动。评估转移性非小细胞肺癌（NSCLC）细胞来源的外泌体对原发性 NSCLC 细胞 EMT 过程的影响。检测 NSCLC 组织中 c-Src 的水平，并评估转移性 NSCLC 细胞来源的外泌体对原发性 NSCLC 细胞外泌体分泌和 EMT 过程的影响。调节 c-Src 的表达，并评估其对外泌体分泌和 EMT 启动的影响。c-Src 在 NSCLC 标本和 EMT 过程增强的 NSCLC 细胞中的表达水平更高。c-Src 的抑制可抑制外泌体的分泌。转移性 NSCLC 细胞来源的外泌体增强了原发性 NSCLC 细胞的迁移和侵袭能力，其作用与 c-Src 过表达相同。c-Src 的抑制抑制了实体瘤的生长和转移以及外泌体的分泌，而注射 c-Src 过表达的外泌体则促进了肺转移。TGF-β1 甚至在 c-Src 敲低的情况下恢复了侵袭和迁移能力。具有高 c-Src 表达的转移性 NSCLC 细胞的外泌体可以增加原发性 NSCLC 细胞中的 c-Src 水平，通过 TGF-β1 途径促进 EMT 过程。
