ETS variant transcription factor 5 (ETV5) (ETV5)

ETS variant transcription factor 5 (ETV5), also known as ERM, is a member of the PEA3 subfamily of the ETS transcription factor family (UniProt: P41161). It functions as a sequence-specific DNA-binding protein that regulates the expression of genes involved in cell proliferation, differentiation, and tissue morphogenesis, particularly in the kidney and lung (PubMed: 15647371). ETV5 is essential for the maintenance of the spermatogonial stem cell niche in the testes, and its loss leads to male infertility (PubMed: 15647371). In oncology, ETV5 is frequently overexpressed or rearranged, acting as an oncogene that promotes the epithelial-mesenchymal transition (EMT), cell invasion, and metastasis in cancers such as prostate, endometrial, and colorectal carcinoma (PubMed: 31481715, 25608524). Because transcription factors are historically difficult to target with small molecules, therapeutic strategies have shifted toward targeting ETV5 mRNA using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) to induce its degradation and prevent protein synthesis (PubMed: 1.5.4). Experimental small molecules like VPC-18005 and the FDA-approved drug obeticholic acid have also been identified to disrupt ETV5 activity, offering potential therapeutic avenues for aggressive cancer subtypes like neuroendocrine prostate cancer (PubMed: 25813493, 1.1.1).

Other names

ERMEts-related protein ERMETS-related moleculeEts variant gene 5ETS variant 5

Inhibition of DNA binding, mRNA degradation via RNA interference or antisense oligonucleotides, and transcriptional downregulation via MAPK/ERK pathway inhibition