C型凝集素LOX-1调控细胞自噬影响肿瘤发生的作用机制研究

食管癌是我国最常见的恶性肿瘤之一，目前仍无有效的靶向治疗药物。C型凝集素LOX-1最初作为ox-LDL的受体被发现，因此以往研究主要集中在内皮细胞表面的LOX-1及其在动脉粥样硬化中的生物学功能，近期被报道与肿瘤发生相关，然而，LOX-1如何影响肿瘤发生以及其中的作用机制还有待进一步被阐明。我们前期研究发现在15种肿瘤中，LOX-1在消化道肿瘤尤其是食管癌中表现出最高差异。本项目拟从细胞自噬角度揭示LOX-1通过与蛋白激酶C受体RACK1相互作用促进食管癌发生的功能和机制。我们还利用表面离子共振技术发现Fucoidan与食管癌细胞表面LOX-1结合，通过靶向LOX-1干预食管癌的发展。该项目研究的开展有助于阐明C型凝集素LOX-1在食管癌发生中的自噬调控作用以及发挥效应的分子机制，为优化岩藻聚糖Fucoidan的抗肿瘤生物学活性以及食管癌靶向治疗提供理论基础和有效策略。

Esophageal cancer is one of the most common malignant tumors in China, and there is still no effective targeted therapy.C-type lectin LOX-1 was initially found as a receptor of ox-LDL，so previous studies focused on LOX-1 of endothelial cell surface and its biological function in atherosclerosis. Recently, it has been reported that LOX-1 is associated with tumorigenesis. However, how LOX-1 affects tumorigenesis remains to be elucidated. Our previous study found that LOX-1 showed the highest difference in esophageal cancer among 15 kinds of tumors, and high expression of LOX-1 suggested poor prognosis in patients with esophageal cancer. This project aims to reveal the function and mechanism of LOX-1 in promoting esophageal cancer by interacting with protein kinase C receptor RACK1 in terms of autophagy. We also found that fucoidan binds to LOX-1 on the surface of esophageal cancer cells by surface ionic resonance technology, and interferes with the development of esophageal cancer by targeting LOX-1. The research of this project will help to elucidate the autophagic regulation of C-type lectin LOX-1 in the occurrence of esophageal cancer and the molecular mechanism of its effect. It will provide theoretical basis and effective strategies for optimizing the anti-tumor biological activity of fucoidan and targeted therapy of esophageal cancer.