TGFβ信号通路的活化在正常成纤维细胞（NFs）转化为肿瘤相关成纤维细胞（CAFs）的过程中起至关重要的作用。课题组前期研究发现胃癌患者血清外泌体中高表达的miR-10b-5p与胃癌侵袭、转移相关，且胃癌细胞释放的外泌体miR-10b-5p可促进NFs转化为CAFs。进一步研究发现：①转录因子Twist1可促进miR-10b-5p的表达；同时，miR-10b-5p可靶向抑制PTEN促进STAT3磷酸化，从而上调Twist1表达。②Twist1可促进TGFβRI过表达；同时，miR-10b-5p可抑制靶基因KLF11和DLG5进而上调TGFβRI表达，活化TGFβ通路。由此，课题组提出假说：胃癌细胞释放的外泌体miR-10b-5p可与Twist1形成正反馈通路，引起TGFβRI过表达，活化TGFβ通路，促使NFs转化为CAFs，促进胃癌侵袭和转移。该假说的阐明将为胃癌的诊疗提供新的理论基础。

The activation of TGFβ signaling pathway is critical for conversion of normal fibroblasts (NFs) into cancer-associated fibroblasts (CAFs). We previously found that high expression level of exosomal miR-10b-5p in serum samples from patients was associated with invasion and migration of gastric cancer. And exosomal miR-10b-5p released from gastric cancer cells could transform NFs into CAFs. In addition, we found: ① Twist1 could induce the expression of miR-10b-5p. Meanwhile, miR-10b-5p could target PTEN, promote the phosphorylation of STAT3 and further induce the expression of Twist1. ② Twist1 could also induce the expression of TGFβRI. While miR-10b-5p could up-regulate TGFβRI via targeting KLF11 and DLG5. Thus, we hypothesized that exosomal miR-10b-5p secreted by gastric cancer cells could be absorbed by fibroblasts and form the positive feedback loop with Twist1, which could positively prompt over-expression of TGFβRI, activate TGFβ signaling pathway, reprogramme NFs into CAFs and subsequently stimulate invasion and metastasis of gastric cancer. We will clarify the hypothesis based on the evaluation of clinical samples, in vitro and in vivo experiments to provide basic research information for the diagnosis and treatment of gastric cancer in the future.