C/EBPß regulates the JAK/STAT signaling pathway in triple-negative breast cancer.

ABSTRACT

C/EBPß is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which consists of a number of b-ZIP transcription factors. Although C/EBPß has been implicated in the development of certain cancers, including breast cancer, it remains unknown whether dysregulation of C/EBPß in breast cancer is subtype-specific. Moreover, the underlying mechanisms by which C/EBPß regulates breast cancer carcinogenesis are not fully understood. Here, we present evidence that C/EBPß is specifically overexpressed in human TNBC samples, but not in non-TNBC samples. C/EBPß depletion dramatically suppressed TNBC cell growth, migration, invasion, and colony formation ability. A subsequent mechanistic study revealed that the JAK/STAT signaling pathway was upregulated in C/EBPß_high TNBC samples compared with C/EBPß_low TNBC samples. C/EBPß ChIP-seq and qPCR were performed to demonstrate that C/EBPß directly binds to and regulates JAK/STAT signaling pathway genes in TNBC. Taken together, our data indicate the oncogenic role of C/EBPß in human TNBC and reveal a novel mechanism by which C/EBPß promotes TNBC carcinogenesis.