转录抑制因子FOXN3在乳腺癌发生发展中的功能及分子机制研究

叉头蛋白转录因子家族（Forkhead-box, FOX家族）共同含有可结合DNA的forkhead结构域，在多种细胞生理活动如代谢、发育、分化、增殖、凋亡、迁移等过程中发挥重要作用。FOXN3是FOX家族成员，具有转录抑制作用。FOXN3在多种肿瘤中表达异常，然而其发挥转录调控功能的分子机制及其如何影响肿瘤的发生发展及转移等生物学行为至今不明。本课题拟在前期工作的基础上，通过遗传学、细胞生物学及分子生物学等手段对FOXN3作为转录因子在全基因组范围内调控的细胞内靶基因进行深入探讨，并解析染色质重塑因子在FOXN3介导的基因转录调控中所发挥的功能。进而以乳腺癌等为模型，初步阐明FOXN3在肿瘤发生发展中的功能及其分子机制。

Forkhead box (Fox) proteins are a family of evolutionarily conserved transcriptional regulators defined by a common DNA-binding domain (DBD) termed the forkhead box or winged helix domain. Fox protein family members are important for a wide spectrum of biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. FOXN3 is a human forkhead transcription factor，which is deregulated in many types of cancers. In this study, we will thoroughly investigate the genome-wide target genes and the underlying molecular mechanisms of FOXN3-mediated transcriptional regulation, and how FOXN3 play a role in breast cancer initiation and progression.