上皮间质转化（EMT）在肿瘤转移中起到重要作用。我们的研究表明组蛋白去乙酰化酶SIRT2在非小细胞肺癌（NSCLC）中可能是一个抑癌基因，上调SIRT2后明显抑制NSCLC增殖，促进其凋亡，并抑制EMT发生。已知TGF-β/Smad通路在调节肿瘤EMT转化中发挥着关键作用，而Smad的乙酰化状态与其活性密切相关，但具体调控机制不详，因此我们提出设想：SIRT2作为一个重要的乙酰化调控基因，通过TGF-β/Smad通路调控NSCLC发生EMT及侵袭转移。为证实该假设，我们首先通过上调SIRT2的表达水平，在体外层面研究SIRT2在TGF-β诱导NSCLC发生EMT转化、侵袭中的作用；其次通过研究SIRT2与Smad的相互作用及其对Smad乙酰化状态的影响，初步阐明SIRT2通过TGF-β/Smad信号通路调控EMT的机制; 最后在小鼠模型、临床标本层面研究SIRT2与Smad对肿瘤转移的影响

Epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis. Our studies have shown that SIRT2, a member of histone deacetylase SIRTUIN family proteins, may be a tumor suppressor gene. We found that overexpression of SIRT2 in Non-small Cell Lung Cancer (NSCLC) cells caused cell proliferation inhibition, cell apoptosis induction and EMT inhibition.TGF-β/Smad signaling pathway plays a key role in the regulation of tumor EMT transformation, and Smad protein acetylation status is closely related to its activity, but the specific regulatory mechanism is unknown. In this study we propose to test the hypothesis that SIRT2 regulates NSCLC EMT, invasion and metastasis by TGF-β/Smad-mediated pathways. To confirm this hypothesis, we first study the role of SIRT2 in TGF-β-induced invasion, metastasis and EMT transformation in NSCLC by upregulating the expression level of SIRT2 in vitro; followed by interaction studies on SIRT2 and Smad acetylation to clarify the regulatary mechanism of EMT by TGF-β/Smad mediated signaling pathways; and finally study the effect of SIRT2 and Smad on tumor metastasis by using mouse models, which will be further evaluated in clinical samples.