代谢失调是肿瘤的重要特征，越来越多的证据表明常见的肿瘤相关基因或信号通路直接参与调控代谢进而影响肿瘤进程。骨桥蛋白（Osteopontin, OPN）是一种分泌型的磷酸化糖蛋白，参与多种恶性肿瘤的发生发展。我们前期研究证实OPN在肝癌的恶性表型中发挥重要作用，可作为预后指标和干预靶点，并初步发现OPN影响肝癌细胞代谢表型，促进葡萄糖摄取、乳酸生成，糖酵解途径增强。进一步通过蛋白质组学分析和免疫共沉淀验证，发现OPN与代谢酶相互作用。因此，本课题拟在已有的系列研究基础上，从转移潜能不同的肝癌细胞、小鼠动物模型以及临床样本等不同层面探讨OPN与肝癌细胞代谢失调的关系，解析OPN介导的代谢重编程在肝癌恶性表型中的功能意义，并揭示其分子调控机制。本课题的研究对进一步深入认识肝癌发生发展的分子机理、探索以代谢酶为基础的肝癌分子分型和靶向治疗的新型药物研发奠定基础。

Altered metabolism is one of the most important phenotypes of cancer cells and is now recognized as a new cancer hallmark. More and more studies revealed that a lot of oncogenes or tumor suppressors are involved in metabolic reprogramming of cancer cells. In our 10 years systematic study, we demonstrated that osteopontin (OPN) played a crucial role in hepatocellular carcinoma (HCC) metastasis. Our preliminary studies found that OPN is closely associated with metabolic signaling pathway. Based on these studies, this project focuses on the influence of OPN on metabolic dysregulation, especially the regulation of the function and metabolic reprogramming. This study may help lay a foundation for answering that critical function of oncogene in metabolic reprogramming of cancer cells and would provide new insights into the molecular mechnism of metastases in HCC.