铁死亡为近年发现的一种特殊的铁依赖性细胞死亡，在肿瘤中发挥不可忽视的作用，但其具体调节机制仍不明确。线粒体电压依赖性阴离子选择通道2（VDAC2）是铁死亡关键调节因子；脂质运载蛋白2（LCN2）及NF-κB为结直肠癌重要调节因子。.我们预实验结果表明，erastin可明显上调结直肠癌细胞中LCN2及VDAC2的表达；VDAC2表达在LCN2过表达的裸鼠成瘤组织中有所上调；TCGA数据库也显示二者呈正相关；干扰NF-κB可逆转干扰LCN2引起的VDAC2表达的下调。我们已发表的文章则表明，LCN2可削弱NF-κB诱导的EMT过程，抑制结直肠癌的进展；而研究表明EMT可抑制铁死亡的发生。我们因此推测LCN2/NF-κB通路可促进VDAC2诱导的结直肠癌铁死亡发生。本课题拟通过体外细胞系，体内小鼠模型及临床样本三方面的研究，探索LCN2诱导铁死亡的分子机制，为结直肠癌的临床治疗提供潜在治疗靶点。

Ferroptosis is recognized as a new form of regulated cell death, which dependents on iron metabolism and plays a crucial role in the development of various cancers. Yet the mechanism is still unclear. Voltage-dependent Anion Channel 2 (VDAC2) is a key regulator of ferroptosis. Lipocalin2 (LCN2) and NF-κB both play an important role in colorectal cancer. Our previous results showed that erastin, a classic inducer of ferroptosis, could upregulate LCN2 and VDAC2 expression in colorectal cancer cells, an dincreased VDAC2 expression is observed in LCN2-overexression xenografts. TCGA database also shows that LCN2 and VDAC2 are positively correlated. Moreover, the downregulated expression of VDAC2 caused by decreasing LCN2 with specific si-RNA could be rescued by si-NF-κB..Our published study showed that LCN2 could attenuate NF-κB-induced EMT process and block the progression of colorectal cancer. Interestingly, researches showed that ferroptosis is inhibited in the progress of EMT..In this study, we will use experimental methods including in vitro experiments in cell lines, in vivo animal experiments and detection in tissue samples to determine whether LCN2/NF-κB signaling pathway could promote ferroptosis through VDAC2, and explore potential targets for clinical treatment of colorectal cancer.