SLIP1/p27kip1调节细胞增殖迁移在肝癌中的意义

在众多CKIs中，p27kip1作为一个cyclin E/CDK2复合物的抑制剂，能够对细胞增殖，分化和恶变起主要调控作用。在肿瘤细胞胞浆中的p27kip1还具有参与RhoA介导的肿瘤侵袭能力。p27kip1功能异常主要受磷酸化修饰、蛋白降解、细胞定位的影响。我们新发现了一个能与p27kip1相互作用的分子SLIP1，初步研究证明两者的表达存在调控关系并与肝癌相关。本研究拟通过研究SLIP1/p27kip1相互作用对p27kip1的磷酸化修饰、蛋白降解、细胞定位影响，研究这种作用与肝癌细胞增殖、迁移的关系。并结合临床标本资料分析，受干预基因裸鼠模型研究，明确SLIP1/p27kip1调节细胞增殖、迁移在肝癌中的意义。本研究不但可以深入了解p27kip1的调节机制；同时将有助于理解这种机制在肝癌发生、发展和预后中的作用，为新的抗癌药物的设计提供靶点。

Among the CKIs, p27kip1 represents an inhibitor of cyclinE/CDK2 complex and plays a central role in cell proliferation, differentiation and malignant transformation. Cytoplasmic p27kip1 appears to participate in RhoA mediated cancer cell invasion. Dysfunction of p27kip1 is regulated by phosphorylation, proteasomal degradation, cellular localization. We have found that SLIP1 could bind with p27kip1, which has not been reported before. Our studies showed that SLIP1 could interact with p27kip1 in hepatocellular carcinoma. We invent to study the effects of SLIP1/p27kip1 on p27kip1 phosphorylation,proteasomal degradation and cellular localization.The results can elucidate the role of interaction between p27kip1 and SLIP1 in proliferation and migration of hepatocellular carcinoma. Furthermore, the role of SLIP1/p27kip1 in regulating cellular proliferation and migration in hepatocellular carcinoma samples and nude mouse model system will also be investigated. This study not only makes a deeper understanding of regulation mechanism of p27kip1, but also helps to demonstrated that in carcinogenesis, development and prognosis in hepatocellular carcinoma, and may provide a potential target for the development of anti-cancer therapy.