Transcription factor SOX-4 (SOX4) (SOX4)

Transcription factor SOX-4 (SOX4) is a member of the SOXC group of SRY-related high-mobility group (HMG) box transcription factors, essential for embryonic development and adult tissue homeostasis [2, 16]. It regulates critical processes such as cell fate determination, differentiation of lymphocytes and osteoblasts, and apoptosis [8, 16]. SOX4 is widely recognized as a potent oncogene, frequently overexpressed or amplified in more than 20 types of human malignancies, including breast, lung, and liver cancers, where it promotes the epithelial-mesenchymal transition (EMT), stemness, and metastasis [16, 17]. Beyond oncology, SOX4 is implicated in inflammatory diseases like rheumatoid arthritis and cardiac hypertrophy [4, 15]. Although traditionally considered "undruggable" due to its lack of a defined small-molecule binding pocket, therapeutic strategies are being explored to inhibit its expression or disrupt its interactions with partners like beta-catenin and p53 [11, 16]. Its role as a master regulator of cancer progression and drug resistance makes it a high-priority target for novel therapeutic interventions [16, 19].

Other names

SRY-box transcription factor 4SRY-box 4Ecotropic viral integration site 16EVI16

SOX4 is primarily targeted through the inhibition of its expression (e.g., by Brevilin A or microRNAs) or the disruption of its transcriptional activity and protein-protein interactions with partners such as beta-catenin, p53, and SMAD3 [11, 16, 18]. It also serves as a mediator of resistance to several chemotherapeutic agents and kinase inhibitors [6, 19].