肿瘤转移是造成非小细胞肺癌（NSCLC）患者死亡的重要原因，但目前尚缺乏有效治疗药物，因此亟需寻找促进NSCLC转移的关键蛋白并发现有效干预手段。我们前期研究发现，AKR1C1可明显促进NSCLC细胞的转移潜能，抑制AKR1C1有效阻断迁移运动；临床样本分析也发现AKR1C1的表达水平与患者生存时间密切相关，提示AKR1C1可能是重要的新型促肿瘤转移蛋白。我们后续研究发现AKR1C1的促转移作用可能与Ran GTPase密切相关。在此基础上，本课题将深入研究AKR1C1促进NSCLC转移的作用及分子机制，阐明其与Ran GTPase的结合模式以及该结合对Ran GTPase核浆运输功能的影响，进一步探索AKR1C1与Ran GTPase结合后促进肿瘤转移的下游信号途径和关键分子，并发现干预两者结合的小分子抑制剂，研究其作为抗肿瘤转移靶点的可能性，为发展全新抗肿瘤转移的治疗策略奠定理论基础。

Metastasis accounts for the major reason of non-small cell lung cancer (NSCLC) patient death, but lacks of effective intervention. Our previous studies indicate that AKR1C1 significantly promotes the NSCLC cell metastasis, and the inhibition of AKR1C1 could suppress the migration and invasion of NSCLC; in addition, the overexpression of AKR1C1 is closely related to the poor prognosis of NSCLC patients, suggesting AKR1C1 may promote metastasis, and this new feature of AKR1C1 has not been reported. Furthermore, we found that AKR1C1-mediated metastasis is closely related to Ran GTPase. On this basis of these preliminary data, the current study will unravel the roles that AKR1C1 played in the process of NSCLC metastasis, clarify the binding sites, binding modes and the regulatory mechanisms of AKR1C1 with Ran GTPase, so as to find the relevant intervention strategies. In addition, elucidate the regulatory mechanism of AKR1C1 on the nuclear import function of Ran GTPase involved in the metastasis of NSCLC, and explore the new signaling pathways and key factors mediating metastasis, as well as the small molecule compounds to interrupt the pathway, thus providing theoretical basis for the exploration of novel anti-metastatic targets and the development of new therapeutic strategies.