SOX4: The unappreciated oncogene

SOX4 is an essential developmental transcription factor that regulates stemness, differentiation, progenitor development, and multiple developmental pathways including PI3K, Wnt, and TGF beta signaling. The SOX4 gene is frequently amplified and overexpressed in over 20 types of malignancies, and multiple lines of evidence support that notion that SOX4 is an oncogene. Its overexpression is due to both gene amplification and to activation of PI3K, Wnt, and TGF beta pathways that SOX4 regulates. SOX4 interacts with multiple other transcription factors, rendering many of its impacts on gene expression context and tissue-specific. Nevertheless, there are common themes that run through many of the effects of SOX4 hyperactivity, such as the promotion of cell survival, stemness, the epithelial to mesenchymal transition, migration, and metastasis. Specific targeting of SOX4 remains a challenge for future cancer research and drug development.