PARK2作为一种E3泛素连接酶，在帕金森病中发挥重要作用。近来，PARK2在肿瘤发生发展中的功能逐步受到重视。我们利用SNP-Chip对神经胶质瘤全基因组拷贝数进行扫描，PARK2位于染色体6q26-27最小同源缺失片段之中，并发现：1)PARK2缺失与EGFR扩增有显著共存关系；2)低表达PARK2与神经胶质瘤预后差呈明显相关性；3)PARK2过表达抑制细胞生长；4)PARK2通过泛素化途径降解EGFR。本课题将进一步从以下几个方面研究肿瘤中PARK2泛素化调控EGFR分子机制及其对肿瘤细胞生长和侵袭的影响：1)PARK2诱导EGFR泛素化的分子机制；2)PARK2对EGFR通路的调控；3)PARK2突变和EGFR突变对两者之间调控关系的影响；4)PARK2与EGFR的关系对肿瘤生长和治疗的影响。通过该研究，将阐明PARK2调控EGFR的分子机制，及其抑制肿瘤细胞生长和侵袭转移的功能。

PARK2, as an E3 ubiquitin ligase, plays an important role in the progress of Parkinson disease. Recently, PARK2 has been assumed to be a tumor suppressor gene in the development of cancer and gradually becoming a hot research field. In previous studies, we used SNP-Chip technique to screen copy number abnormality of the whole genome in GBMs, and found that PARK2 localized in the common minimum deleted region (CMDRs) of 6q26-27, which contained only four genes. At the same time, we found that in GBM specimens and cell lines, PARK2 presented lower expression, and patients had a significantly shortened survival time with low PARK2 expression. In recent work, we pointed out PARK2 was associated with the EGFR degradation through ubiquitination pathway, and suggested that PARK2 was involved in the malignant transformation and tumor cell growth by regulating the EGFR. In this study, we will take glioma as a cell model to investigate the regulation mechanism between PARK2 and EGFR: 1) the mechanism of PARK2 inducing ubiquitination of EGFR; 2) regulation of PARK2 on EGFR pathway; 3) the effect of mutation in both of PARK2 and EGFR on correlativity between these two genes; 4)the effects of PARK2 on cell growth and invasion through EGFR pathway, as well as therapeutic strategy of cancer dependences on the correlativity of PARK2 and EGFR. Our studies will help to better clarify the mechanism of PARK2 in the regulation of the cell malignant transformation and inhibition of cell growth.