FOXC2促进乳腺癌转移的表观遗传学机制研究

Metastasis is the major cause of death in breast cancer. Many genes have been identified to be responsible for the development of breast cancer,including FOXC2. FOXC2 has been reported to be a key mediator of epithelial mesenchymal transition(EMT) and contribute to the progression and metastasis in breast cancer. we demonstrated that FOXC2 is associated with KDM4A and MTA1, and promtes the invasion of breast cancer cells in vitro.These preliminary data indicated that FOXC2 plays a curial role in breast cancer metastasis.But the underlying mechanism of how FOXC2 regulate and influence on breast cancer development and progression need to be further elucidated. We propose here to screen and identify the potential transcriptional targets for FOXC2/KDM4A/MTA1(NuRD) that may operate in metastasis of breast cancer. Our research will reveal molecular mechanism and extend the biological function of FOXC2 in tumor invasion and metastasis,supporting the pursuit of FOXC2 as a potential target for breast cancer intervention.

既往研究证明FOXC2能促进乳腺癌等多种恶性肿瘤的侵袭与转移，然而其分子作用机制尚未完全阐明。本课题以乳腺癌为研究对象，通过免疫亲和质谱分析等技术发现FOXC2能与KDM4A和NuRD复合体的MTA1有直接相互作用，提示FOXC2可能通过表观遗传调控途径促进乳腺癌的侵袭与转移；在此研究基础上，我们进一步利用ChIP-seq技术高通量检测FOXC2蛋白复合体在乳腺癌中可能调控的关键靶基因结合区域，通过分析、筛选和鉴定各自和共同可能作用的相关信号通路和关键下游靶基因，并分别从体外和体内实验详细阐述和证明FOXC2蛋白复合体和相关的下游靶基因在乳腺癌转移过程的作用及其分子机制，以此来揭示FOXC2蛋白促进乳腺肿瘤转移的分子作用新机制，为乳腺癌的临床干预提供新的靶点和治疗方向。

已有研究显示FOXC2在参与肿瘤的发生、转移等过程发挥着重要作用，然而其分子作用机制尚未完全阐明。本课题以乳腺癌为研究对象，通过免疫亲和质谱分析等技术发现FOXC2能与KDM4A和NuRD复合体的MTA1直接相互作用，提示FOXC2可能通过表观遗传调控途径促进乳腺癌的侵袭与转移；在此研究基础上，我们进一步利用ChIP-on-chip技术高通量检测和生物信息学等技术帅选到FOXC2/KDM4A/MTA1蛋白复合体在乳腺癌中可能调控的关键下游靶基因，并从体外实验详细阐述和证明FOXC2/KDM4A/MTA1复合体共同调控介导乳腺肿瘤细胞EMT的关键因子E-cadherin，此来揭示FOXC2蛋白促进乳腺肿瘤转移的分子作用新机制，为乳腺癌的临床干预提供新的靶点和治疗方向