腹膜转移严重影响胃癌患者生存，但机制仍需探讨。近年来的研究表明，原发灶释放的信号，转移部位转移前“龛”(pre-metastatic niche，PMN)的形成是定向转移的关键。我们的前期研究证实胃癌来源外泌体能诱导腹膜间皮细胞向PMN特征性细胞—癌相关成纤维细胞(cancer associated fibroblasts, CAFs)转变，促进胃癌腹膜转移发生；我们利用前期建立的腹膜高转移胃癌细胞系，筛选出泛素连接酶UBE3B可能是外泌体携带的关键分子，过表达UBE3B的胃癌细胞来源的外泌体显著提高间皮细胞向CAFs转变的能力，及其与胃癌细胞的粘附能力；进一步实验发现Cbl-b可能是其靶分子。我们提出：胃癌释放的外泌体通过携带UBE3B，靶向间皮细胞Cbl-b，诱导间皮细胞向CAFs转化，形成腹膜特异性PMN，促进胃癌腹膜转移。本研究结果将为阐明胃癌腹膜转移机制提供新的科学数据。

Peritoneal metastasis affects the overall survival of gastric cancer patients, and the mechanisms need to be further investigated. Recent studies have shown that the signals released by cancer cells, and the formation of pre-metastatic niche (PMN) are key elements determined the directional metastasis. Our previous studies have demonstrated that gastric cancer-derived exosomes promoted peritoneal metastasis of gastric cancer by inducing the transformation of peritoneal mesothelial cells (PMCs) to cancer-associated fibroblasts (CAFs), which was considered as the characteristics of the PMN. By using the high peritoneal metastatic gastric cancer cell line we have already established, we further identified E3 Ubiquitin ligase, UBE3B, might be one of the key molecules carried by exosomes. Exosomes derived from gastric cancer cells overexpressing UBE3B can induce the transformation of PMCs to CAFs, and significantly improve the ability of adhesion to gastric cancer cells. Further experiments showed that Cbl-b might be the potential target of UBE3B. In summary, we propose that gastric cancer derived exosomal UBE3B, induced PMCs transformed into CAFs to form peritoneal-specific PMN by targeting Cbl-b in mesothelial cells, and eventually, promoted peritoneal metastasis of gastric cancer. The results of this study will further elucidate the mechanism of gastric cancer peritoneal metastasis.