ETV4

ETV4, also known as a member of the PEA3 subfamily of ETS transcription factors, is encoded by the ETV4 gene. It belongs to the ETS family, a group of transcription factors that regulate gene expression in development and various cellular processes. ETV4 is related to other PEA3 family members such as ETV1 and ETV5.

ETV4 binds to DNA at ETS-binding sites, which typically include a GGAA core sequence. Through these sites, it regulates the transcription of a range of target genes involved in development, cell migration, and invasion. In many contexts, ETV4 influences genes linked to extracellular matrix remodeling, including matrix metalloproteinases, contributing to cellular movement and tissue remodeling.

Regulation of ETV4 activity is connected to signaling pathways, especially the Ras/MAPK pathway. ERK-mediated phosphorylation can enhance ETV4’s DNA-binding and transcriptional activity. Its function can be modulated by interactions with coactivators such as p300/CBP and by microRNAs, which can influence its expression levels and activity.

In development, ETV4 participates in tissue morphogenesis and organ formation in multiple species, with disruption leading to developmental abnormalities in some models. In disease, overexpression or amplification of ETV4 is associated with increased metastatic potential and poorer prognosis in several cancers, including breast, colorectal, and prostate cancers. As a result, ETV4 is a focus of research as a potential biomarker and therapeutic target, with studies exploring approaches to modulate its activity.