申请人前期研究证实转化生长因子β（TGFβ）在胃癌转移过程中发挥重要作用，血清剥离反应蛋白（serum deprivation protein response, SDPR）是TGFβ的潜在下游靶点。目前SDPR在胃癌中的作用及其机制仍不清楚。前期通过基因芯片分析，我们发现SDPR可能调控胃癌脂代谢。预实验证实SDPR受TGFβ调控，通过与ERK发生蛋白相互作用，调控ERK/PPARα信号轴，转录水平调节肉碱棕榈酰基转移酶1A（carnitine palmitoyltransferase 1A，CPT1A），参与胃癌脂肪酸氧化。由此我们提出SDPR是连接脂代谢和胃癌转移的重要分子。本项目拟采用分子生物学、分子病理学方法，全方位阐明SDPR调控胃癌转移的机制，提供TGFβ通过SDPR发挥生物学功能的直接证据，为确立TGFβ/SDPR/CPT1A轴作为晚期胃癌患者临床治疗靶点提供科学依据。

Our previous study found that transforming growth factor beta (TGFβ) plays important role in mediating metastasis of gastric cancer(GC)，and serum deprivation protein response (SDPR) is a potential downstream of TGFβ. The role and the underlying mechanism of SDPR in GC are still unclear. Though gene chip analysis, we found that SDPR might regulate lipid metabolism in GC. In the preliminary experiments, we confirmed that SDPR was regulated by TGFβ, and regulated the ERK/PPARα axis by directly interacting with ERK, thereby regulating the carnitine palmitoyltransferase 1A（CPT1A）and participating in lipid metabolism of GC. Therefore, we propose that SDPR as a key intracellular molecule linking lipid metabolism and GC metastasis.. Using molecular biology and molecular pathology methods, we aim to fully clarify the mechanism of SDPR in regulating GC metastasis, and provide direct evidence that TGFβ exerts biological functions through SDPR, and supply scientific basis for establishing TGFβ/SDPR/CPT1A axis as a novel target for clinical therapy of patients with advanced GC.