The ETS family of oncogenic transcription factors in solid tumours

Findings over the past decade have identified aberrant activation of the ETS transcription factor family throughout all stages of tumorigenesis. Specifically in solid tumours, gene rearrangement and amplification, feed-forward growth factor signalling loops, formation of gain-of-function co-regulatory complexes and novel cis-acting mutations in ETS target gene promoters can result in increased ETS activity. In turn, pro-oncogenic ETS signalling enhances tumorigenesis through a broad mechanistic toolbox that includes lineage specification and self-renewal, DNA damage and genome instability, epigenetics and metabolism. This Review discusses these different mechanisms of ETS activation and subsequent oncogenic implications, as well as the clinical utility of ETS factors.