SIX homeobox 4 (SIX4)

SIX homeobox 4 (SIX4) encodes a transcription factor from the homeobox protein family, specifically the SIX class, characterized by a homeobox DNA-binding domain and a SIX protein–protein interaction domain[1][2][3]. The Drosophila homolog (DSix4) is expressed primarily in the gonad and mesodermal tissues; in mammals, SIX4 is important for differentiation and maturation of neuronal cells and organogenesis[1][2][3]. SIX4 directly regulates gene expression for developmental processes and cell fate specification, and can interact with similar transcriptional targets and protein partners found within its family. Aberrant expression of SIX4 is frequently observed in various cancers, promoting tumor initiation, growth, invasion, angiogenesis, and metastasis—often through pathways such as ERK/NF-κB and enhanced expression of oncogenes like YAP1, MET, and VEGF-A[2]. These properties have led to the investigation of SIX4 as a biomarker for cancer diagnostics and prognosis[2].

Other names

Homeobox protein SIX4AREC3Sine oculis homeobox homolog 4