白细胞介素6（IL-6）可通过诱导上皮间质转化（EMT）促进肿瘤侵袭转移，但其分子机制尚不明确。我们前期研究发现，IL-6诱导结直肠癌细胞EMT伴随着硫氧还蛋白1（Trx-1）的核转运及S100P表达上调；初步证实Trx-1与p-STAT3存在相互作用，敲除STAT3可以抑制IL-6诱导的Trx-1核转运；并且Trx-1可以通过调节S100P的表达促进结直肠癌细胞的EMT及侵袭转移。因此，我们推测IL-6可能通过磷酸化激活STAT3诱导Trx-1核转运，进而激活S100P的转录，诱导EMT促进结直肠癌侵袭转移。本研究拟利用Trx-1不同表达水平或活性状态的细胞模型及knock-in小鼠，采用多种分子和细胞生物学技术及炎症相关肠癌小鼠模型等方法，阐明IL-6刺激下Trx-1的核转运机制，并揭示其促进结直肠癌EMT和侵袭转移的作用机理，为探索结直肠癌的转移机制和寻找有效的治疗靶点奠定基础。

The pro-inflammatory cytokine interleukin-6 (IL-6) in tumor microenvironment has been suggested to induce epithelial-mesenchymal transition (EMT) and invasion and metastasis of colorectal cancer (CRC). However, the underlying molecular mechanisms remain elusive. Our pilot data showed that Trx-1 nuclear translocation was induced and the expression of S100P gene was significantly upregulated during IL-6-driven EMT process. Our data also showed that Trx-1 interacts with p-STAT3 protein. IL-6 induced Trx-1 nuclear translocation was inhibited by knockdown of STAT3 in CRC cells. Moreover, Trx-1 could promote CRC cell EMT, migration and invasion by upregulating S100P expression. Therefore, we hypothesize that Trx-1 nuclear translocation is induced by IL-6 through activation of the phosphorylation of STAT3, and then induces EMT, invasion and metastasis of CRC through upregulating S100P gene expression. To test this hypothesis, we will investigate the role of Trx-1 nuclear translocation during IL-6 induced EMT and invasion and metastasis of CRC using a cellular model with different expression level or activity status of Trx-1 and transgene mice by a variety of molecular and cellular biology techniques and mouse model of colitis-associated cancer. The goal of the proposed experiments is to elucidate the functions and molecular mechanisms of Trx-1 nuclear translocation during IL-6 induced EMT and invasion and metastasis of CRC, with hope of understanding the underlying mechanism of CRC metastasis and seeking effective therapeutic targets.