上皮-间充质转化（EMT）是肿瘤细胞转移过程的启动环节。肿瘤患者常处于慢性心理应激状态，体内以去甲肾上腺素（NE）为代表的压力相关激素水平升高。我们前期研究发现，NE能通过促进肿瘤细胞表达TGF-β，直接诱导体外肿瘤细胞发生EMT。然而体内环境中慢性应激对EMT的作用及机制，目前尚未见报道。NE可通过上调乏氧诱导因子HIF-1α促进赖氨酰氧化酶（LOX）的表达。文献报道，LOX可诱导细胞外基质重塑，继而促使肿瘤细胞发生EMT。因此，我们完全有理由推测，在体内慢性应激环境下NE可通过TGF-β直接促进肿瘤细胞发生EMT；另一方面通过上调LOX促进细胞外基质重塑，进一步促进EMT的发生。本项目拟模拟肿瘤患者所处的“慢性应激状态”构建荷瘤小鼠模型，观察慢性应激对体内肿瘤细胞EMT的作用，并探讨其可能的机制。据我们所知，目前国内外尚未见从这一角度研究EMT的报道。

The epithelial-mesenchymal transition (EMT) plays a critical role in the initiation of tumor metastasis. Frequently, cancer exposes patients to chronic psychological stressful situations, which causes the elevated levels of stress-related hormones like norepinephrine (NE) in the body. In our previous study, it was observed that NE could directly induce EMT of tumor cells in vitro through promoting expression of transforming growth factor beta (TGF-β). However, it has not been confirmed how chronic stress affects EMT in vivo. NE facilitates the expression of Lysyl oxidase (LOX) by up-regulating hypoxia-inducible factor 1α (HIF-1α). It was reported that LOX could induce the remodeling of extracellular matrix thus promoting the EMT of tumor cell. Therefore, we speculate that under the state of chronic stress in vivo, NE could directely promote the occurence of EMT through TGF-β. This is the one hand. On the other hand, NE could promote extracellular matrix remodeling through up-regulating LOX, which would further facilitate the process of EMT. In this project, we intend to establish tumor-bearing mice models to mimic the chronic stress state of cancer patients, to explore the effects and the underlying mechanisms of chronic stress on EMT in vivo. So far as we know, there is no literature reported regarding EMT from this perspective.