骨肉瘤（OS）复发转移是影响患者生存的主因。本团队发现DGKZ (甘油二酯激酶IV zeta)在OS细胞及组织高表达，瘤组织的表达明显高于瘤旁组织，复发转移瘤组织的表达明显高于原发瘤；沉默DGKZ能抑制OS细胞增殖、促进凋亡并抑制裸鼠移植瘤生长和转移；Microarray及IPA信号网络分析示DGKZ影响MYC信号通路多个关键分子的表达，q-PCR及Western blot证实，沉默DGKZ后关键分子的表达明显改变。液相色谱-串联质谱法结合Co-IP证实，DGKZ与ERK1/2存在相互协同作用。因此我们提出：OS复发转移涉及DGKZ-ERK1/2-MYC信号通路的调控。本项目拟从临床、功能及机制相关性三方面入手，采用蛋白芯片、激光共聚焦、功能回复实验和Co-Ip 等方法进一步证实DGKZ与ERK1/2及MYC的具体作用方式，阐明其在OS复发转移中的作用机制，寻找有价值的生物学标志。

Osteosarcoma(OS) is the primary malignant bone tumor that most commonly affects .children, adolescents, and young adults. However, survival rates continue to be unsatisfactory in the metastatic and relapse setting. Therefore, it is imperative to discover a novel target for more effective therapeutic interventions towards osteosarcoma. Diacylglycerol kinase zeta (DGKZ) is a recently identified gene potentially associated with certain human carcinogenesis. However, the expressional correlation and functional importance of DGKZ in osteosarcoma is still unclear. In this study, expression of DGKZ was firstly confirmed in OS sample tissues and correlated with poor prognosis in OS patients and was obviouly higher in metastatic OS tissue than it's expression in local OS tissue. Depletion of DGKZ by shRNA inhibited osteosarcoma cell proliferation and promoted cell apoptosis in vitro. In vivo, DGKZ silencing also suppressed xenograft tumor formation as determined by bioluminescence imaging and weight/volume measurements. Meanwhile, Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA) demonstrated that DGKZ knockdown resulted in a decreased activity of MYC pathway, and several target genes expression in MYC pathway were altered, including CCND1, CDKN2B,CDK6,PCNA and EGR1. Furthermore, immunoprecipitation coupled with mass spectrometry (IP-MS) analysis was used to identify proteins that interacted with DGKZ in OS cells and revealed ERK1/2, a key MYC-interactor, to associate with DGKZ. Together, our data shows that DGKZ acts an oncogene in osteosarcoma via its possible interaction with ERK1/2 and MYC pathway. This project is designed to investigate and testify relationship between DGKZ and ERK1/2 plus MYC in recurrence and metastasis of OS in order to find out a potential target for osteosarcoma treatment.