染色质重塑复合物SWI/SNF家族在肿瘤中具有近20%的突变率，其亚单位ARID1A在各种恶性肿瘤中突变率极高。近年来针对ARID1A缺失的功能研究十分火热，揭示了ARID1A在多种恶性肿瘤中的抑癌功能及作用机制。然而ARID1A在食管癌中突变率很低，其在食管癌中的功能和调控机制尚未有研究报道。泛素化与去泛素化是调控蛋白稳定性的关键修饰类型，我们前期研究结果发现ARID1A在鳞状细胞癌中受泛素蛋白酶体调控，说明泛素化异常很可能是ARID1A在鳞状细胞癌中失活的关键因素。进一步质谱分析结合文库筛选发现泛素化酶TRIM32及去泛素化酶USP11调控ARID1A蛋白的稳定性，其异常表达可能促进鳞状细胞癌的发生发展。本课题立足于揭示ARID1A在鳞状细胞癌中非突变性质的失活机制，并据此为鳞状细胞癌的临床诊断及治疗提供依据。

SWI/SNF chromatin remodeling complexes show nearly 20% mutation in cancer, and its variant subunit ARID1A shows very high mutation rates among various cancer types. In recent years, scientists focused on the study of ARID1A and revealed its tumor suppressive functions and molecular mechanisms. However, the mutation rate of ARID1A in esophageal squamous cell carcinoma (ESCC) remains quite low. The biological function and the underlying mechanism of ARID1A in ESCC has not been determined. Ubiquitination and deubiquitination are key post-translational modulations that control the stability of protein. Our previous results showed that ARID1A was modulated by the ubiquitin-proteasome system in ESCC, the abnormal regulation of ARID1A ubiquitination might be the key event that causes ESCC development and progression. Through mass spectrum analysis together with cDNA library screening, we identified TRIM32 and USP11 to be key E3 ligase and deubiquitinase that modulates the ubiquitination of ARID1A in ESCC. Overexpression or knockdown of TRIM32 or USP11 could affect the progression of ESCC via modulating ARID1A stability. This study will focus on revealing of the unique non-mutational inactivation mechanism of ARID1A in ESCC and seeking for promising insights of clinical transformation.