内吞复合体蛋白HCRP1对肝癌的影响及作用机理

Recently, endocytosis has been regarded as a long-term mechanism of signal attenuation via receptor clearance from cell surface. It is thus predicted to play a causative role in hyperproliferative conditions and foremost cancer. The human Hepatocellular Carcinoma Related Protein 1 (HCRP1) is a growth inhibitory protein and down-regulated in liver cancer tissues. It also be a subunit of Endosomal Sorting Complex Required for Transport-1(ESCRT-I) that mediates receptor down-regulation. Therefore it is necessary to study the function of HCRP1 in endocytosis and cancer formation. The research project here includes three aspects: (1) the effects of HCRP1 on hepatocelluar carcinogenesis. (2) The role of HCRP1 in endosomal sorting and degradation of membrane receptors. (3) The interactions between HCRP1 and TSG101, a co-member of ESCRT-1. Our purpose is to understand whether the reduction of HCRP1 could result in developing cancer, and to find mechanisms, which might be linked to endocytic control, for HCRP1 in promotion of cancer.

近十年来，随着细胞内吞作用的分子机制逐步被揭示，内吞作用对肿瘤发生发展的影响也成了研究热点。我们鉴定的HCRP1蛋白具有抑癌功能，又是ESCRT-I复合体的成员，参与内吞作用，是研究内吞分选与肿瘤发生的绝好材料。为此，本项目拟在三方面开展研究：（1）HHCRP1对肝癌发生发展的影响；（2）HCRP1在内吞分选过程中的功能和受其影响的膜受体通路；（3）HCRP1与内吞分选复合体核心蛋白TSG101的相互作用。这些研究内容是在我们前期工作的基础上展开，已积累了一定的数据和研究系统。通过上述研究，我们将证明HCRP1在肝癌中异常表达，这种异常可能导致肿瘤发生。了解HCRP1低表达诱发癌变是否与细胞内吞作用受损有关，与膜受体不能正常降解有关。本项目的实施对于阐明HCRP1在细胞内吞中的分子机制以及在肝癌发生发展中的作用具有重要的意义，并为HCRP1在肝癌早期诊断和治疗中的应用提供分子基础。