食管鳞癌是我国高发的恶性肿瘤之一，其死亡率居全部恶性肿瘤的第四位。已有研究显示，自噬和凋亡抑制对于食管鳞癌细胞的生存十分重要，但对食管鳞癌细胞自噬和凋亡调控的机制仍有待进一步研究。PIWIL2是一种新发现的多功能癌睾丸蛋白。我们最近发现PIWIL2在食管鳞癌中高表达并与患者预后不良相关。进一步研究显示PIWIL2能在食管鳞癌细胞中与IκB激酶IKK作用并增强其激酶活性。过表达PIWIL2能够促进食管鳞癌细胞自噬并抑制细胞凋亡，而IKK抑制剂能够回复PIWIL2对自噬和凋亡的调控。本研究拟在此基础上进一步研究PIWIL2在ESCC细胞中通过与IKK相互作用对肿瘤细胞自噬和细胞凋亡的调控的作用机制，探索PIWIL2对食管鳞癌细胞治疗抵抗的影响及其分子机理。这将阐明癌睾丸蛋白PIWIL2在食管鳞癌中通过IKK对自噬和凋亡新的调控机制，及其对自噬的调控在食管鳞癌化疗抵抗的作用研究也具有重要意义。

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in China, and the fourth most common cause of death from cancer. Previous studies showed that autophagy and apoptosis inhibition are critical for the survival of ESCC cells. However,the underlying mechanisms remain to be clarified. Recently, we found that PIWIL2, a novel cancer testis protein, is highly expressed in ESCC and associated with poor prognosis. Our further study showed that PIWIL2 can interact with IκB Kinase (IKK) and enhance its activity. Overexpression of Piwil2 can promote autophagy and inhibit apoptosis, and this regulation can be rescured by treatment of IKK inhibitor. These findings suggested that PIWIL2 can regulate autophagy and apoptosis via IKK pathway in ESCC cells. Based on which, a series of experiments such as Transmission electron microscope, immunoprecipitation, ChIP, cell models and animal models will be performed, and we will investigate the mechanism through which PIWIL2 regulates autophagy and apoptosis involving chemotherapy resistance in ESCC. This research will reveal novel mechanism of PIWIL2 regulating autophagy and apoptosis in ESCC, providing novel insights in autophagy regulation involving chemotherapy resistance in ESCC.