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Last update 08 May 2025

SOX18

Last update 08 May 2025

Basic Info

Synonyms

SOX18, SRY-box transcription factor 18, Transcription factor SOX-18

Introduction

Transcriptional activator that binds to the consensus sequence 5'-AACAAAG-3' in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis. Activates transcription of PROX1 and other genes coding for lymphatic endothelial markers. Plays an essential role in triggering the differentiation of lymph vessels, but is not required for the maintenance of differentiated lymphatic endothelial cells. Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX17. Interaction with MEF2C enhances transcriptional activation. Besides, required for normal hair development.

Drugs associated with SOX18

SOX18(Gertrude)

Target

SOX18

Mechanism

SOX18 modulators

Active Org.

Gertrude Biomedical Pty Ltd.

Originator Org.

Gertrude Biomedical Pty Ltd.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SOX18

100 Translational Medicine associated with SOX18

0 Patents (Medical) associated with SOX18

265

Literatures (Medical) associated with SOX18

01 Apr 2025·Journal of Clinical Investigation

An endothelial SOX18–mevalonate pathway axis enables repurposing of statins for infantile hemangioma

Article

Author: Nasim, Sana ; Qi, Yanfei ; Francois, Mathias ; Kozakewich, Harry ; Sun, Mingwei ; Borgelt, Luke ; Lekwuttikarn, Ramrada ; Tan, Jerry Wei Heng ; Teng, Joyce ; Brouillard, Pascal ; Wylie-Sears, Jill ; Holm, Annegret ; Graus, Matthew S ; Vikkula, Miikka ; Mulliken, John B ; Jain, Ashish ; Chung, Long ; Sun, Liang ; Alvarez-Harmon, Maya ; Bischoff, Joyce

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis, and regression. Propranolol, the mainstay of treatment, inhibits IH vessel formation via a β-adrenergic receptor-independent off-target effect of its R(+) enantiomer on endothelial SOX18 - a member of the SOX (SRY-related HMG-box) family of transcription factors. Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss and gain of function of SOX18 confirmed it is both necessary and sufficient for R(+) propranolol suppression of the MVP, including regulation of sterol regulatory element-binding protein 2 (SREBP2) and the rate-limiting enzyme HMG-CoA reductase (HMGCR). A biological relevance of the endothelial SOX18-MVP axis in IH patient tissue was demonstrated by nuclear colocalization of SOX18 and SREBP2. Functional validation in a preclinical IH xenograft model revealed that statins - competitive inhibitors of HMGCR - efficiently suppress IH vessel formation. We propose an endothelial SOX18-MVP axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. The pleiotropic effects of R(+) propranolol and statins along the SOX18-MVP axis to disable an endothelial cell-specific program may have therapeutic implications for other vascular disease entities involving pathological vasculogenesis and angiogenesis.

24 Feb 2025·Theranostics

The m6A modification of SOX18 leads to increased PTX3 and cardiomyocyte pyroptosis in sepsis-induced cardiomyopathy

Article

Author: Zhu, Hanzhao ; Liu, Jincheng ; Xue, Chao ; Zhang, Bin ; Zhang, Liyun ; Duan, Weixun ; Qiao, Xinan ; Wang, Longteng ; Jiang, Liqing ; Sun, He ; Yi, Wei ; Peng, Xiangyan ; Yang, Jian

Rationale: Sepsis-induced cardiomyopathy (SIC) is a rapidly progressing condition with poor prognosis in the absence of effective therapeutic interventions. Cardiomyocyte pyroptosis is a critical factor contributing to cardiac dysfunction in SIC. Currently, research on this mechanism remains unclear. Methods: We performed LPS-induced primary mouse cardiomyocyte modeling and mouse SIC modeling. Through mRNA-Seq, we found significant pyroptosis in the cardiac tissue of SIC mice. Further confocal microscopy and immunoprecipitation results confirmed that PTX3 is an important participant in cardiomyocyte pyroptosis. We then used ChIP and dual-luciferase reporter assays to confirm that SOX18 exerts a transcriptional repression effect on PTX3. M6A-Seq and RNA stability assays confirmed that the m6A modification mediated/recognized by RBM15/YTHDF2 is a crucial factor in the changes of SOX18 in SIC. Results: Our experiments demonstrated that the abnormally elevated PTX3 in SIC plays a key role in mediating pyroptosis. Under physiological conditions, PTX3 transcription is repressed by SOX18. However, during septic cardiomyopathy, SOX18 stability is compromised by RBM15/YTHDF2-mediated m6A modification, leading to increased PTX3 levels and the subsequent induction of cardiomyocyte pyroptosis. Conclusion: In summary, we have delineated the RBM15/YTHDF2-SOX18-PTX3 axis in SIC. It provides a new approach for the treatment of cardiomyocyte pyroptosis in SIC and for improving prognosis.

01 Jan 2025·Cancer Reports

The Transcription Factor SOX18 Inhibitor Small Molecule 4 Is a Potential Treatment of Cancer‐Induced Lymphatic Metastasis and Lymphangiosarcoma

Article

Author: Zimmermann, Martin M. ; Hirche, Christoph ; Will, Patrick A. ; Kneser, Ulrich ; Koll, Katja K.

ABSTRACTBackgroundMalignant tumors release growth factors, promoting lymphangiogenesis in primary tumors and draining sentinel lymph nodes, ultimately facilitating lymph node metastasis. As a malignant lymphatic tumor entity, lymphangiosarcomas are characterized by low survival rates and limited treatment options. The transcription factor SOX18 plays a crucial role in both lymphatic endothelial cell differentiation and cancer‐induced lymphangiogenesis.AimsIn this in vitro study, we investigated the potential therapeutic effect of a small molecule called Sm4, which inhibits SOX18, on lymphatic endothelial and lymphangiosarcoma cells in vitro.Methods and ResultsHuman dermal lymphatic endothelial cells (HDLECs), lymphangiosarcoma cells (MO‐LAS), and other endothelial cell lines were cultured. We found that Sox18 exhibited high mRNA expression levels in both HDLEC and MO‐LAS. Sm4 treatment decreased the Sox18 expression level at the mRNA and protein levels in both HDLEC and MO‐LAS significantly, a phenomenon confirmed through immunofluorescence images. Additionally, Sm4 treatment suppressed the expression of key lymphatic phenotype markers (Prox1, Flt4, and Lyve1) and hindered migration in both HDLEC and MO‐LAS, all while maintaining cell viability.ConclusionThese findings suggest that targeting SOX18 with Sm4 may hold potential as a therapeutic strategy for lymphangiosarcoma and cancer‐induced lymphatic metastasis. Further in vitro studies are warranted to investigate the mechanisms and conduct dose–response analyses to evaluate Sm4's potential as a targeted therapy for lymphangiosarcoma and cancer‐induced lymphangiogenesis in the future.

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