我们以往的研究证明，Fascin蛋白在食管癌中异常高表达，介导癌细胞丝状伪足形成，在癌细胞分裂增殖与侵袭移动中发挥促癌功能，是食管癌重要功能蛋白。最近我们进一步研究发现，该蛋白K471赖氨酸残基是乙酰化修饰位点，对食管癌细胞分裂增殖与侵袭转移发挥负调控作用；食管癌组织中，与配对的正常食管上皮相比，其乙酰化修饰水平明显低下，乙酰化与去乙酰化修饰循环严重失衡，与食管癌恶性进展密切相关。然而有关是何种乙酰基转移酶与去乙酰基酶，负责Fascin-K471乙酰化与去乙酰化修饰循环这一重要科学问题，目前尚不知晓。为此，本项目拟首先系统鉴定食管癌中Fascin-K471乙酰基转移酶与去乙酰基酶，接下来重点研究这些酶发挥作用的分子机制，同时探讨其临床意义，证明“Fascin-K471乙酰化与去乙酰化修饰循环失衡促食管癌发生发展”新科学理论假说，为以Fascin为靶点，开展食管癌临床转化研究提供理论依据。

In our previous studies, Fascin was found to be abnormally highly expressed and work as a critical functional protein of esophageal cancer (EC) that mediates cell filopodia formation and prompts cell proliferation, motility and invasion. In recent study, we found that Lysine 471 (K471) of Fascin was acetylated, which inhibited the proliferation, motility and invasion of esophageal carcinoma cells. Compared with paired normal tissues, the acetylation level of Fascin K471 was lower in tumor tissues, leading to a serious unbalance between acetylation and deacetylation of Fascin K471, which strongly associated with EC progression. However, the remaining important question, which acetyltransferase/deacetylase is in charge of keeping balance of Fascin K471 acetylation/deacetylation, is still unknown. Therefore, in this project, we will first systematically identify the acetyltransferase and deacetylase of Fascin K471 in EC, and secondly focus on molecular mechanisms of acetyltransferase/deacetylase action, furthermore, explore its clinical significance, finally test the scientific hypothesis "unbalance of Fascin K471 acetylation/deacetylation promotes initiation and progression of EC”, and ultimately offer theoretical basis to use Fascin as a target for clinical transition in EC therapy.