Revisiting GATA4 - Multifunctional transcriptional factor of oncogenesis

The GATA family of zinc finger DNA-binding transcription factors plays a crucial role in regulating genes responsible for embryogenesis, cellular differentiation, and normal physiological development. This family comprises six members, designated as GATA1 to GATA6, with GATA4 being of particular significance due to its prominent tissue-specific functions. Mutations in GATA4 have been extensively linked with human congenital diseases affecting the heart, lungs, and reproductive system. It is regulated by post-translational modifications, notably phosphorylation at serine 105 by ERK and p38MAPK kinases. The expression and oncogenic/tumor-suppressive roles of GATA4 in cancer have sparked substantial research interest. GATA4 forms essential regulatory complexes with its family members, GATA5 and GATA6 during early myocardial development, and with transcriptional cofactors such as TBX5 and NKx2-5, underscoring its importance in maintaining cellular and molecular homeostasis. Emerging evidence highlights that dysregulated GATA4 expression contributes not only to developmental abnormalities but also to cancer progression, where it may exhibit oncogenic or tumor-suppressive functions depending on the tissue context. These dual roles highlight GATA4 as a crucial molecular node in pathways governing cell survival, proliferation, and tumorigenesis. Therefore, understanding the multifaceted biological implications of GATA4 is indispensable for identifying novel therapeutic targets. This review aims to comprehensively summarize the functional significance of GATA4 in the pathophysiology of developmental disorders and diverse cancers.