Delineating the tumour-regulatory roles of EYA4

Eyes absent homolog 4 (EYA4) is a protein that regulates many vital cellular processes and organogenesis pathways. It possesses phosphatase, hydrolase, and transcriptional activation functions. Mutations in the Eya4 gene can cause sensorineural hearing loss and heart disease. In most non-nervous system cancers such as those of the gastrointestinal tract (GIT), hematological and respiratory systems, EYA4 acts as a putative tumor suppressor. However, in nervous system tumors such as glioma, astrocytoma, and malignant peripheral nerve sheath tumor (MPNST), it plays a putative tumor-promoting role. EYA4 interacts with various signaling proteins of the PI3K/AKT, JNK/cJUN, Wnt/GSK-3β, and cell cycle pathways to exert its tumor-promoting or tumor-suppressing effect. The tissue expression level and methylation profiles of Eya4 can help predict the prognosis and anti-cancer treatment response among cancer patients. Targeting and altering Eya4 expression and activity could be a potential therapeutic strategy to suppress carcinogenesis. In conclusion, EYA4 may have both putative tumor-promoting and tumor-suppressing roles in different human cancers and has the potential to serve as a prognostic biomarker and therapeutic agent in various cancer types.