Sox Protein Function in Development and Cancer
Summary
The SOX family of transcription factors encompasses twenty members characterised by a conserved high-mobility group (HMG) DNA-binding domain. These proteins act as architectural regulators of chromatin, orchestrating cell-fate decisions, stem-cell maintenance and tissue differentiation during embryonic development, including neural, vascular and gonadal lineages. In the adult, they sustain tissue homoeostasis and contribute to regeneration. Dysregulation of SOX proteins in cancer can confer either oncogenic or tumour-suppressive functions in a context-dependent manner, influencing cell proliferation, invasion, epithelial-mesenchymal transition, stemness and resistance to therapy. Mechanistically, SOX factors modulate transcriptional programmes via direct DNA binding, protein–protein interactions and epigenetic regulation, intersecting key pathways such as Wnt/β-catenin and cell-cycle control. These insights have highlighted SOX proteins as potential biomarkers for prognosis and as therapeutic targets, with emerging strategies to inhibit pathogenic SOX activity demonstrating proof-of-principle in preclinical models.
Research from Nature Portfolio
Studies have unveiled unique features of SOXE transcription factors. It has been shown that SOX8, SOX9 and SOX10 engage in cooperative dimerisation on palindromic DNA motifs with variable spacing, mediated by interactions between the dimerisation and HMG domains. This multifaceted binding mechanism expands the diversity of target-gene regulation, providing a structural basis for context-dependent control of developmental programmes and tumour-associated gene networks.
Sox Protein Function in Development and Cancer publication trend
The graph below shows the total number of articles in sox protein function in development and cancer across all publications each year (not limited to Nature Index journals).
Technical terms
Transcription factor: Protein that governs gene expression by binding specific DNA sequences.
High-mobility group (HMG) domain: Conserved region that enables DNA binding and bending by SOX proteins.
Dimerisation: Assembly of two protein monomers into a functional complex, often enhancing DNA-binding specificity.
Epithelial-mesenchymal transition (EMT): Process by which epithelial cells acquire migratory mesenchymal characteristics.
Epigenetic regulation: Control of gene expression via DNA methylation or histone modification without altering the DNA sequence.
References
- SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains. Scientific Reports (2015).
- SOX on tumors, a comfort or a constraint?. Cell Death Discovery (2024).
- SOX7 inhibits the malignant progression of bladder cancer via the DNMT3B/CYGB axis. Molecular Biomedicine (2024).
- SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer. Cancers (2023).
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