SOX2在乳腺癌细胞干性维持中转录调控机制研究

乳腺癌是女性最高发的癌症类型。乳腺癌干细胞是乳腺癌发生发展的基础。已有研究表明SOX2是乳腺癌细胞干性维持的关键因子，在乳腺癌发生发展中发挥关键作用，然而在乳腺癌细胞中SOX2的表达调控机制却不清楚。我们课题组初步研究结果表明SOX2启动子区含有GATA转录因子识别元件，在乳腺癌中非典型GATA转录因子TRPS1与SOX2表达负相关，TRPS1通过招募去乙酰化核小体重塑酶复合体（NuRD complex）在乳腺癌细胞中抑制SOX2的表达。本项目的研究中我们将在前期的工作基础上综合应用生物信息学、生化与分子生物学和细胞生物学等方法，结合小鼠模型和临床样本数据分析，从转录组学、蛋白质组学和表观遗传学等方面，进一步深入研究乳腺癌细胞中SOX2表达的转录调控机制及该机制在乳腺癌干细胞干性维持和乳腺癌发生发展中的作用，具有重要意义。

Breast cancer is a major cancer type in women. Breast cancer stem cells determine breast tumorigenesis and breast cancer development. Although SOX2 was reported to play a key role in breast tumorigenesis and breast cancer development via functioning as the key transcriptional factor in maintenance of stemness of breast cancer cells, it was largely unknown about how the expression of SOX2 was transcriptionally regulated in breast cancer cells. We found that SOX2 promoter contains the GATA transcription factor binding consensus sequence element. In breast cancers, the SOX2 expression level was found to be significantly negatively correlated with the expression of the atypical GATA transcription factor TRPS1. Our preliminary data shows that TRPS1 represses SOX2 expression via recognizing the GATA transcription factor binding consensus sequence element in the SOX2 promoter and recruiting Nucleosome Remodeling Deacetylase (NuRD) complex in breast cancer cells. In current proposal, we will further explore the mechanism of transcription regulation of SOX2 in maintenance of stemness of breast cancer cells during breast tumorigenesis and breast cancer development. We intend to uncover how SOX2 expression was transcriptional regulated in breast cancer to improve the understanding of molecular mechanism in stemness maintenance of breast cancer cells.