The Roles of STAT3 and STAT5 in Breast Cancer
Alexandra Elizabeth Temple, Sarah R. Walker
Abstract
STAT3 and STAT5 are two related transcription factors involved in normal mammary gland development and function. However, inappropriate activation of either STAT3 or STAT5 has been shown to play a role in breast cancer, where STAT3 is highly associated with aggressive tumors and STAT5 is associated with lower-grade and more differentiated tumors. As transcription factors, STAT3 and STAT5 transcriptionally regulate genes involved in proliferation, migration, and chemoresistance. Furthermore, STAT3 and STAT5 transcriptional activity can be modulated by several known cofactors, where these cofactors can influence how STAT3 and STAT5 interact with DNA and with other proteins, ultimately affecting transcriptional function. Interestingly, STAT3 and STAT5 share a subset of overlapping target genes and can compete for DNA binding of shared binding sites. These STATs have also been shown to have opposing effects on overlapping target gene expression, where gene expression is determined by the STAT protein occupying the promoter. This is particularly interesting since STAT5-driven breast tumors are molecularly distinct from STAT3-driven breast tumors. Furthermore, concurrent activation of STAT3 and STAT5 is associated with more favorable tumor types compared to tumors with activated STAT3 alone, suggesting that the relationship between these two STATs is critical. Developing a better understanding about the roles that STAT3 and STAT5 play in breast cancer will be important for successful treatment in the future.