Figure 2. FOXC1 function and activity in human diseases.

FOXC1 has been shown to play an integral role in development and adulthood, with both increased and decreased FOXC1 function linked to abnormal disease phenotypes. For example, due to profound defects in ocular development, hydrocephaly, cardiac organogenesis and skeletal anomalies, homozygous null Foxc1 mice do not survive past birth [16]. Mutations in FOXC1 are shown to hinder FOXC1-DNA binding activity, FOXC1 protein level and stability, as well as FOXC1 translocation to the nucleus – all of these defects resulting in Axenfeld-Rieger Syndrome (ARS). More recently, FOXC1 has been demonstrated to have a key role in cancer progression. Contrary to the reduced FOXC1 function observed in ARS, recent studies are linking escalated FOXC1 protein levels to the development of more aggressive phenotypes in cancers such as breast cancer, HCC, and endometrial cancer.