ETV5

ETV5, or Ets variant 5, is a transcription factor in the Ets family, belonging to the PEA3 subfamily along with ETV1 and ETV4. The ETV5 protein contains an ETS DNA-binding domain that recognizes the GGAA/T core motif and functions primarily as a transcriptional regulator. Its activity is modulated by signaling pathways that respond to growth factors, and phosphorylation by MAP kinase cascades can influence its transcriptional activity and stability.

Expression of ETV5 is detected in a range of tissues, with notable roles during development. It has been linked to embryonic brain and sensory organ development and to processes governing tissue morphogenesis, migration, and differentiation. In the mammary gland, ETV5 has been implicated in ductal development and lactation, and in other organs it can influence morphogenesis and organ size.

In disease, dysregulation of ETV5—through gene amplification, fusion events, or altered signaling—has been associated with cancer progression in various contexts. Overexpression of ETV5 has been observed in breast cancer, prostate cancer, and other tumor types and is often linked to increased invasive potential and metastasis, in part via upregulation of matrix metalloproteinases and other target genes. However, its role is context dependent, and ETV5 can also have anti-proliferative effects in certain settings.

Therapeutic approaches targeting ETS factors are an area of active research, though specific inhibitors of ETV5 remain under development. Understanding ETV5's downstream targets and regulatory networks continues to be important for interpreting its contributions to development and disease.