Functional analysis of key molecule of breast cancer stem cells

我们发现HRG/ErbB信号是调节乳腺癌干细胞特性的关键分子机制。ErbB信号通过PI3K/NF-kappaB通路维持乳腺癌干细胞的特性，提示生长因子信号和炎症反应通路之间的串扰在这种调控中很重要。此外，作为PI3K信号的下游介质，IGF2信号是维持乳腺癌干细胞特性所必需的。此外，通过微阵列分析鉴定的HRG和IGF特征与乳腺癌的分级和预后（如转移或复发）密切相关。这些观察结果表明，这些生长因子信号通过维持乳腺癌干细胞特性在乳腺癌恶性进展中发挥重要作用。

We identified HRG/ErbB signaling as a key molecular mechanism on regulating breast cancer stem cell properties. ErbB signaling maintains breast cancer stem cell properties via PI3K/NF-kappaB pathway, suggesting that crosstalk between growth factor signaling and inflammatory response pathway is important for such regulation. Moreover, IGF2 signaling is required for maintenance of the breast cancer stem cell properties as a downstream mediator of PI3K signaling. Also, HRG signature and IGF signature identified by microarray analysis is strongly associated with both breast cancer grade and prognosis such as metastasis or relapse. These observations suggest that these growth factor signaling have important roles on malignant progression of breast cancer through maintenance of breast cancer stem cell properties.