肿瘤转移是大肠癌治疗失败的主要原因。血管生成与脂代谢异常是癌转移的重要特征，但两者关系研究较少。我们发现载脂蛋白APOC2在肠癌组织中表达上调，并在转移灶中表达更高；过表达APOC2促进肿瘤侵袭及血管生成，激活脂蛋白脂酶，刺激VEGFA表达。此外高通量数据提示STAT3/MAPK是APOC2潜在的下游靶标。据此，我们推测：APOC2可能参与脂代谢激活STAT3/MAPK-VEGFA信号通路诱导血管生成，促进肿瘤转移。因此，本项目拟①沉默和过表达APOC2观察其在肠癌转移中的作用；②酶活性检测与质谱分析APOC2对脂代谢关键酶及产物的影响；③共聚焦、WB等探讨APOC2通过STAT3/MAPK调控血管生成的途径；④PDX模型验证APOC2促进脂代谢和血管生成诱导转移的机制，结合公共数据库和临床大样本验证其临床价值。本研究可望阐明APOC2诱导血管生成促进肿瘤转移机制，为大肠癌防治提供新思路。

Tumor metastasis is the main reason for the failure of treatment for colorectal cancer. Angiogenesis and abnormal lipid metabolism are important features of cancer metastasis, but the relationship between them has not been well clarified. We found that the expression of apolipoprotein APOC2 was up-regulated in colorectal cancerous tissues, and was higher in metastatic tumor tissues compared with primary cancer samples. Over-expressing APOC2 in colon cancer cells promotes tumor invasion and angiogenesis, and activates lipoprotein lipase(LPL) and stimulates the level of VEGFA. Additionally, high-throughput data suggest that STAT3/MAPK is a potential downstream target of APOC2. Thus, we speculate that APOC2 may participate in lipid metabolism inducing tumor angiogenesis via activating STAT3/MAPK-VEGFA pathway to promote tumor metastasis. Therefore, this study intends to 1) observe APOC2’s function in colon cancer metastasis by silencing and over-expressing this gene in colon cancer cells; 2) detect the activity of key enzymes of lipid metabolism, and the lipid metabolite using mass spectrometry in APOC2-silenced/over-expressed colon cancer cells; 3) explore APOC2’s effect on tumor angiogenesis by activating STAT3/MAPK pathway by laser confocal microscopy and western blot; 4) verify the mechanism of APOC2’s promoting tumor metastasis by regulating lipid metabolism and angiogenesis through using patient-derived xenograft(PDX) model, combined with public database and large samples of colonic tumor tissues and paired normal tissues, and investigate its clinical value. It is expected to clarify the mechanism of APOC2’s induction of angiogenesis to promote tumor metastasis and provide new insights in the prevention and treatment of colorectal cancer.