β半乳糖苷α-2,6-唾液酸转移酶1(ST6GAL1)主要负责N型糖链末端α2,6-唾液酸的合成，该酶表达的上调与肿瘤发生发展密切相关，但具体调控机制尚不明确。我们新发现了食管癌中高表达的ST6GAL1可以抑制Hippo信号通路，初步研究证明两者存在正反馈调控并与食管癌相关，并且我们筛选出了参与此调控的潜在性协同膜蛋白。基于此，本课题提出“相关膜蛋白介导ST6GAL1与Hippo信号通路间的交互调控参与食管癌发病机制”的假说。本研究拟揭示ST6GAL1具体通过修饰哪些特定靶蛋白介导调节Hippo通路、活化的YAP对ST6GAL1表达的影响及其中的分子机制，并结合裸鼠模型和临床标本，明确ST6GAL1、YAP及相关膜蛋白调控食管癌增殖和转移的作用。本研究可以深入了解ST6GAL1与Hippo信号通路间的调节机制及其与食管癌发生发展和预后的关系，为寻找生物标记物和临床干预靶点提供新的视角。

β-galactoside α2,6 sialyltranferase 1 (ST6GAL1), which primarily catalyzes terminal α2,6 sialylation on N-glycans, is upregulated in multiple types of cancers and highly correlated with tumor malignancies, however, the underlying mechanisms are poorly understood. In our preliminary work, we have revealed the effects of up-regulated ST6GAL1 on Hippo signaling pathway and cell behaviors in esophageal cancer cells, during which, there is a ST6GAL1-YAP positive feedback mechanism. Also, we have screened several sialylated candidates which may mediate the regulation of ST6GAL1-Hippo pathway. Based on these results, we hypothesized that indicate membrane proteins mediate the positive autofeedback loop of ST6GAL1-Hippo signaling pathway to drive esophageal cancer progression. To elucidate the molecular mechanisms of ST6GAL1 and Hippo-YAP signaling in esophageal cancer cell proliferation and migration, we are planning to identify the specific glycoproteins modulated by ST6GAL1 in the regulation of Hippo pathway and investigate the effect of activated YAP on the expression of ST6GAL1. Furthermore, the regulatory mechanisms between ST6GAL1, YAP and target proteins will be verified by using animal models as well as clinical samples. In conclusion, this study will clarify mechanistic roles of ST6GAL1-Hippo signaling in tumorigenesis, development and prognosis, which may provide a potential target for development of bio-marker and anti-cancer therapy.