FoxM1在上皮间质转化（EMT）介导的肺腺癌转移中的作用及其机制研究

It has been noted that epithelial mesenchymal transition (EMT) plays a key role in the initiation of tumor cell metastasis.However, it's not clear for the underlying molecular mechanisms of tumor EMT process and related signal transduction network. We previously identified that Fox transcription factor family member FoxM1 might be a key modulator in the EMT signaling pathway of malignances. It may transactivate the PDGFA/PDGFR signaling pathway and then involve in the initiation of metastasis of lung adenocarcinoma through EMT process, which still need to be further elucidated detailedly. This study aims to explore the underlying intrinsic molecular mechanisms of FoxM1-PDGFA/PDGFR-EMT signaling pathway and the role in metastasis of lung adenocarcinoma.Our study may further explore the molecular mechanism of metastasis of lung adenocarcinoma and identify critical molecular target for the prognosis and therapy, which may have important theoretical significance and potential value.

上皮间质转化(EMT)是已知的启动肿瘤细胞转移过程的关键生物学现象,目前对调控肿瘤EMT过程的分子机制和级联信号转导网络尚未清楚。本课题组前期发现Fox转录因子家族成员FoxM1是潜在的EMT通路关键信号蛋白,可能通过活化PDGFA/PDGFR通路参与EMT介导的肺腺癌癌转移始动过程，但具体作用机制有待明确。据此，本课题拟在前期工作基础上利用体内外实验首次验证FoxM1－PDGFA/PDGFR－EMT信号通路的内在调控网络和促癌转移的作用机制，这对于进一步明确肺腺癌转移的分子机制和寻找可用于转移风险评估和治疗的分子靶点具有较重要的理论意义和潜在应用价值。

肺癌是世界范围内发病率死亡率第一位恶性肿瘤，目前临床缺少有效的预后预测及分子治疗靶点。上皮间质转化(EMT)是已知的启动肿瘤细胞转移过程的关键生物学现象,目前对调控肿瘤EMT过程的分子机制和级联信号转导网络尚未清楚。Fox转录因子家族成员FoxM1是近年来发现的重要原癌基因，本项目的研究聚焦在FoxM1调控肺腺癌亚型的功能机制研究，本课题组研究发现FoxM1是潜在的EMT通路关键信号蛋白，发现FoxM1通过转录水平调控上皮间质转化（EMT）的关键信号节点SNAIL，影响肺癌EMT过程，进而参与肺腺癌的增殖、侵袭转移等恶性生物学行为，对寻找新的诊治靶点提供了创新性理论依据。同时提出FoxM1- SNAIL-EMT的信号通路转导机制，有助于深入理解肿瘤转移的基础机制。这一研究成果对于进一步明确肺腺癌转移的分子机制和寻找可用于转移风险评估和治疗的分子靶点具有较重要的理论意义和潜在应用价值。