In conclusion, we demonstrate a previously unknown interaction between FOXL2 and GATA4, together with SMAD3, and these transcription factors can modulate the promoter activity of the key target genes involved in GCT cell proliferation and survival, such as CCND2. Moreover, the data further strengthens the role of SMAD3 in human GCT pathogenesis, as previously suggested by studies in GCT mouse models and human GCT cell line. This evidence concerns the gene SMAD3 and granular cell tumor.