胞外囊泡在局部和远程细胞间的通信中起着关键作用，参与了各种生理和病理过程。肿瘤来源的胞外囊泡在肿瘤发生中至关重要，但其分泌机制尚不清楚。尤其是介导多囊泡体（MVB）与细胞质膜（PM）融合的SNARE蛋白质仍存在争议。在本研究中，我们发现Syntaxin-4、SNAP-23和VAMP-7是负责MCF-7乳腺癌细胞中胞外囊泡分泌的SNARE蛋白质，并发现这些SNARE蛋白的复合物能够在体外驱动膜融合。删除MCF-7细胞中的任何一个这些SNARE蛋白并不影响MVB的生成和转运，表明它们在MVB-PM融合中具有特定的作用。此外，Syntaxin-4、SNAP-23和VAMP-7在HeLa子宫颈癌细胞和A375黑色素瘤细胞中的胞外囊泡分泌中发挥了相同的作用，表明它们在胞外囊泡分泌中具有保守的功能。此外，删除4T1乳腺癌细胞中的VAMP-7能有效抑制胞外囊泡的分泌，并且导致小鼠模型中肿瘤生长和肺部转移显著减弱，表明VAMP-7可能作为乳腺癌的一种新治疗靶点。© 2023 The Authors. Journal of Extracellular Vesicles由Wiley Periodicals, LLC代表国际胞外囊泡学会出版。

Exosomes play crucial roles in local and distant cellular communication and are involved in various physiological and pathological processes. Tumour-derived exosomes are pivotal to tumorigenesis, but the precise mechanisms underlying their secretion remain elusive. In particular, the SNARE proteins that mediate the fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in tumour cells are subject to debate. In this study, we identified syntaxin-4, SNAP-23, and VAMP-7 as the SNAREs responsible for exosome secretion in MCF-7 breast cancer cells and found that a SNARE complex consisting of these SNAREs can drive membrane fusion in vitro. Deletion of any of these SNAREs in MCF-7 cells did not affect MVB biogenesis and transportation, indicating their specific involvement in MVB-PM fusion. In addition, syntaxin-4, SNAP-23, and VAMP-7 play equivalent roles in exosome secretion in both HeLa cervical cancer cells and A375 melanoma cells, suggesting their conserved function in exosome secretion. Furthermore, deletion of VAMP-7 in 4T1 mammary carcinoma cells efficiently inhibited exosome secretion and led to significant attenuation of tumour growth and lung metastasis in mouse models, implying that VAMP-7 may hold promise as a novel therapeutic target for breast cancer.© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.