脂代谢异常与肿瘤的发生发展密切相关，靶向脂代谢是一种极具前景的肿瘤治疗策略。深入理解肿瘤脂代谢的分子调控机制，是优化当前肿瘤代谢治疗策略的关键。SREBP1是启动脂质从头合成途径的关键转录因子，也是当前肿瘤脂代谢领域的研究热点。内皮生长因子EGF与其受体EGFR的结合可以增强SREBP1转录活性，促进其对下游脂质新生关键酶的转录，调节肿瘤脂代谢及增殖。本课题组前期研究表明EGF/EGFR活化可以促进SREBP1蛋白的甲基化修饰，参与肿瘤增殖调控。本研究拟以分子生物学检测技术、质谱分析法及代谢显像手段，多角度揭示EGF/EGFR信号通路通过甲基化修饰调控SREBP1转录活性的分子机制，并明确EGF/EGFR信号通路对SREBP1的甲基化作用对肿瘤脂代谢及增殖表型的影响，寻找参与SREBP1转录活性调控并可被有效干预的生物标记，为临床制定肿瘤脂代谢靶向治疗策略提供重要的科学依据。

Lipometabolic disorder is a key feature of cancer metabolism. Targeting lipid metabolism is confirmed as a promising strategy for tumor therapy. Thorough understanding to the molecular mechanisms in regulating tumor lipid metabolism is essential to optimize the current treatment strategies. SREBP1 is the key transcription factor triggering de novo lipogenesis, as well as the hotspot in the field of cancer metabolism research. The activation of EGF/EGFR pathway was proved promoting the transcriptional activity of SREBP1 to its target genes, involving in tumor metabolism and proliferation. We also found EGF/EGFR pathway could regulated the methylation level of protein SREBP1 to control the growth of tumor. In this study, we try to reveal the molecular mechanisms of EGF/EGFR pathway mediated methylation of SREBP1, as well as the biological effects of EGF/EGFR-induced methylated SREBP1. This study will provide both rationale and target biomarkers regulating the activity of SREBP1 for cancer metabolic therapy.