GT36是我们新近发现的一种蛋白，其生物学功能尚未报道。TGF-β1参与胚胎发育、炎症、肿瘤发生等生命活动。我们前期工作发现GT36增强TGF-β1启动子转录活性，上调其表达，进而促进乳腺癌细胞的EMT进程，增强其转移能力。我们还发现GT36介导的TGF-β1上调引起p-Smad2上升，激活经典的TGF-β/Smad通路，导致MCF10A细胞由表皮形态向间质形态转变。这一过程伴随着一系列EMT marker的变化，如E-cadherin的下调和N-cadherin和Vimentin的上调。这些结果提示GT36在乳腺癌细胞的EMT发生中发挥重要的作用。本项目旨在探讨GT36与TGF-β1启动子作用并调节其表达的机制，阐明其对乳腺癌细胞EMT发生、侵袭转移和裸鼠体内成瘤的影响及作用机制。此外，将检测临床乳腺癌标本探索GT36与乳腺癌恶性程度和预后的相关性，为寻找乳腺癌新的治疗靶点提供理论依据。

GT36 protein is a newly identified protein in our earlier work; its biological functions have not yet been studies. TGF-β1 participates in a wide range of biological activities including embryonic development, inflammation, carcinogenesis and tumor metastasis, etc. We discovered in our pre-experiments that GT36 was able to interact with the TGF-β1 promoter to stimulate its transcription activity resulting in the upregulation of TGF-β1. This process led to the enhanced potentiality of the epithelial mesenchymal transition (EMT) and migration in breast cancer cells. Moreover, the GT36-mediated TGF-β1 upregulation caused a rise in p-Smad2, which led to the activation of the canonic TGF-β/Smad signaling. This was accompanied by a series of changes that mark the EMT process, including the change from the epithelial morphology to mesenchymal morphology of the cells, as well as the downregulation of the epithelial marker E-cadherin, and upregulation of the mesenchymal markers N-cadherin and Vimentin. These previous data suggest that GT36 plays a critical role in EMT in breast cancer cells. The aims of this study are to investigate the molecular mechanisms by which GT36 regulates TGF-β1 promoter activity and expression, and to explore the roles of this regulatory process in breast cancer cell EMT and invasion; as well as in the tumorigenesis in nude mice model. In addition, we intend to study the correlation between the GT36 and the malignancy and prognosis of breast cancer by analyzing the clinic pathological samples. Perspectively, this study will provide molecular basis for the development of GT36 as a potential target for breast cancer therapy.