脂质代谢与肿瘤的生长和转移密切相关。本课题预实验利用CRISPR/cas9基因敲除文库系统、小鼠肺转移模型、二代测序等技术，筛选与乳腺癌转移相关的脂质代谢基因，发现候选基因NSDHL可能通过影响TGFβ信号通路进而促进乳腺癌转移。本课题拟在前期工作基础上，采用细胞、动物及临床标本等实验进一步明确NSDHL在乳腺肿瘤转移中的作用；采用IP-mass、RNA-seq、生物信息学等技术揭示与NSDHL相互作用的蛋白及其共同调控乳腺癌转移的分子机制；采用代谢组学等方法，揭示NSDHL信号通路相关脂质代谢物调控乳腺癌转移的作用及机制；确定NSDHL及其代谢产物在乳腺癌诊治中的临床意义，探索其与乳腺癌类型、淋巴结转移、病人生存率等指标之间的临床规律。本课题有助于全面揭示NSDHL及其代谢产物促进乳腺癌转移的分子机制，有助于发现乳腺癌转移过程中新的分子靶点，对于指导临床治疗乳腺癌具有实际应用价值。

Deregulation of lipid metabolism is associated with cancer metastasis. Our pre-experiments demonstrated that NSDHL showed higher expression in highly metastatic breast cancer cells than primary cancer cells by CRISPR/Cas9 systems，lung metastasis model in mice, next generation sequencing and other methods. Besides, inhibition of NSDHL significantly inhibited breast cancer migration and invasion by regulating TGFβ pathway, suggesting that NSDHL may play an important role in breast cancer metastasis. In this study, we will further study the effect of NSDHL on breast cancer metastasis by cellular assays, animal experiments and clinical investigation. We will clarify the mechanism of NSDHL and its binding protein in breast cancer metastasis by adopting IP-mass,RNA-seq, Bioinformatics and other methods. We may reveal the new metabolites and its role in NSDHL pathway by adopting Metabonomics and other methods. Furthermore, we will confirm how NSDHL and its metabolites clinically relates to breast cancer metastasis, survival rate and prognosis. This research is helpful to explore the relevance between NSDHL pathway and breast cancer metastasis and cast light on a potential new target molecule which may be a potent diagnostic marker or an anti-metastatic agent for breast cancer.