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SRY-box transcription factor 17 (SOX17)
- Target
- SOX17
- Molecular classification
- Transcription factor, SRY-related HMG-box protein, SOXF subfamily member (with SOX7, SOX18)
01
Overview
SRY-box transcription factor 17 (SOX17) is a member of the SOXF subfamily of high mobility group (HMG) box transcription factors that binds DNA within the minor groove and bends it, using unique charge-distribution interaction platforms[1]. SOX17 is a master regulator of early cell fate, directing definitive and extraembryonic endoderm differentiation, programming vascular and germ cell lineages, and acting as a tumor suppressor through antagonism of the Wnt/β-catenin pathway[2][3][4]. In cancer, SOX17 promoter hypermethylation leads to its silencing, increased proliferation, and metastatic phenotypes, making its methylation status a promising biomarker for malignancy. SOX17 also plays essential roles in hematopoiesis, vascular biology, and neural development, but has no directly approved small molecule therapies, with therapeutic strategies focused on restoring its expression or function.
- Other names
- Transcription factor SOX-17SOX17SRY-box 17SRY-related HMG-box transcription factor SOX17PPH7VUR3
02
Mechanism of action
Reactivation of SOX17 expression through demethylation of promoter region to restore tumor suppressor function.
03
Biological functions
Regulation of vertebrate embryonic developmentDetermination of endodermal cell fateSpecification of primordial germ cell-like cellsProgramming of hemogenic endothelium and arterial identityOligodendrocyte differentiation (neural development)Regulation of Wnt/β-catenin signalingTumor suppressionRegulation of Notch1 signaling and hematopoietic activity (stem cell, fetal hematopoiesis)Endothelial differentiation and vessel formation
04
Disease associations
Cancer (tumor suppressor role, especially in colorectal, hepatocellular, esophageal, lung, gastric, breast cancers)Pulmonary arterial hypertensionIntracranial aneurysmSpermatogenesis dysfunctionCardiovascular disease (heart and vessel development)Gallbladder abnormalitiesHematopoietic disordersNeural disorders (oligodendrocyte development)
05
Safety considerations
Therapeutic challenges in restoring SOX17 function due to epigenetic silencing in cancerPotential off-target effects of epigenetic drugs (like 5-aza-2’-deoxycytidine)Specific targeting of transcription factors like SOX17 remains complex—risk of developmental disruption if aberrantly activated
06
Interacting drugs
5-aza-2’-deoxycytidine (DNA methyltransferase inhibitor that demethylates SOX17 promoter)
1 more in the full profile.
07
Biomarkers
SOX17 promoter methylation (disease stratification, early cancer detection, prognosis)SOX17 protein expression (tumor tissue, circulating tumor cells, or cell-free DNA)
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