Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer

The PEA3 subfamily is a subgroup of the E26 transformation-specific (ETS) family. Its members, ETV1, ETV4, and ETV5, have been found to be overexpressed in multiple cancers. The deregulation of ETV1, ETV4, and ETV5 induces cell growth, invasion, and migration in various tumor cells, leading to tumor progression, metastasis, and drug resistance. Therefore, exploring drugs or therapeutic targets that target the PEA3 subfamily may contribute to the clinical treatment of tumor patients. In this review, we introduce the structures and functions of the PEA3 subfamily members, systematically review their main roles in various tumor cells, analyze their prognostic and diagnostic value, and, finally, introduce several molecular targets and therapeutic drugs targeting ETV1, ETV4, and ETV5. We conclude that targeting a series of upstream regulators and downstream target genes of the PEA3 subfamily may be an effective strategy for the treatment of ETV1/ETV4/ETV5-overexpressing tumors.