SOX4 (SRY (sex determining region Y)-box 4)
2009-01-01 David L Satinover , Chris A Moskaluk AffiliationDept. of Pathology, Dept. of Biochemistry, Molecular Genetics P.O. Box 800214 University of Virginia Health System Charlottesville, VA 22908, USA
DNA/RNA
Description
This intronless gene encompasses 4789 base pairs.
Transcription
The mRNA transcript is 4789 base pairs.
Proteins
Description
The mRNA encodes a 47.3 kDa protein consisting of 474 amino acids.
Expression
SOX4 appears to be fairly ubiquitously expressed at low levels in most adult tissues, with high levels found mostly in T lymphocytes. Its expression is up-regulated in many cancer types relative to benign tissue of origin (Rhodes et al., 2004).
Localisation
Nucleus.
Function
SOX4 is a member of the class I SRY-related HMG-box family of transcription factors. It has been shown to be involved in determination of cell fate and the regulation of embryonic development of many organ systems including heart (Restivo et al., 2006; Schilham et al., 1996), pancreas (Lioubinski et al., 2003; Wilson et al., 2005) and brain (Cheung et al., 2000; Hong and Saint-Jeannet, 2005). SOX4 has been shown to be a transcriptional activator in lymphocytes (van de Wetering et al., 1993) and facilitates B and T cell differentiation (Schilham et al., 1996; Schilham et al., 1997). SOX4 gene expression is up-regulated in many tumor types, with experimental evidence suggesting that this contributes to cellular transformation (Liu et al., 2006; Shin et al., 2004), control of apoptosis (Liu et al., 2006; Pramoonjago et al., 2006; Aaboe et al., 2006; Ahn et al., 2002) and/or a metastatic phenotype (Liao et al., 2008; Tavazoie et al., 2008).
Homology
SOX4 is part of a family of Sox transcription factors that share significant homology. SOX4 is in the Group C Sox homology group that includes SOX11, SOX22 and SOX24. SOX4 shares the highest degree of homology with SOX11 (Bowles et al., 2000).
Implicated in
Entity name
Adenoid Cystic Carcinoma (ACC)
Note
Gene expression profiling using micro arrays has shown SOX4 is one of the most up-regulated genes in ACC, relative to non-neoplastic tissue of origin (Frierson et al., 2002). Immunohistochemistry analysis confirms the up-regulation of SOX4 in primary ACC tumors compared to normal tissue (Pramoonjago et al., 2006).
Disease
ACC is the second most common malignant salivary gland tumor, representing 28% of malignant submandibular gland tumors.
Entity name
Bladder Cancer
Note
Whole genome expression profiling of 166 bladder tumors and 27 normal samples showed SOX4 up-regulated 5 fold in the tumors. When over-expressed in the bladder cell line HU609, SOX4 strongly impaired cell viability and promoted apoptosis (Aaboe et al., 2006).
Prognosis
A correlation was found between strong SOX4 expression levels and increased patient survival.
Entity name
Breast Cancer
Note
MicroRNA miR335 has been shown to regulate Sox4 levels and is frequently found lost in primary tumors of breast cancer patients who relapse (Tavazoie et al., 2008). In experimental model systems, it appears that SOX4 is a primary gene product associated with metastasis and migration.
Entity name
Leukemia
Note
SOX4 transcript is found in high levels in B-ALL and T-ALL, but not in AML, CML, CLL, Sezary syndrome, or T cell prolymphocytic leukemia (Mallampati et al., 2008). Retroviral tagging in mouse models suggests a functional role for SOX4 in hematologic malignancies (Shin et al., 2004; Suzuki et al., 2002; Lund et al., 2002).
Entity name
Lung Cancer
Note
SOX4 is upregulated is a significant percentage of lung cancers (Bangur et al., 2002; Friedman et al., 2004) and antibodies to this protein can be found in the serum of lung cancer patients (Friedman et al., 2004).
Entity name
Hepatocellular Carcinoma
Note
Experimental manipulation of SOX4 in hepatocellular carcinoma cell line models suggests that SOX4 is pro-apoptotic in this tumor type (Ahn et al., 2002). Paradoxically, another group found that knocking down SOX4 expression in a hepatocellular carcinoma cell line decreased tumorigenicity (Liao et al., 2008).
Entity name
Medulloblastoma
Note
SOX4 is significantly overexpressed in medulloblastoma compared to normal cerebellum and ependymoma (de Bont et al., 2008; Yokota et al., 2004).
Prognosis
A trend was found towards increased survival with increased levels of expression of SOX4.
Entity name
Prostate Cancer
Note
SOX4 has been show to be over-expressed in prostate tumor samples by microarray analysis, real-time PCR and immunohistochemistry. Additionally, stable transfection of Sox4 into non-transformed prostate cells form colonies in soft agar, suggesting SOX4 can be a transforming oncogene.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16585165 | 2006 | SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization. | Aaboe M et al |
| 12216117 | 2002 | Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A(2) and delta(12)-PGJ(2). | Ahn SG et al |
| 12032850 | 2002 | Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis. | Bangur CS et al |
| 11071752 | 2000 | Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. | Bowles J et al |
| 10925158 | 2000 | Roles of Sox4 in central nervous system development. | Cheung M et al |
| 14978140 | 2004 | Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen. | Friedman RS et al |
| 12368205 | 2002 | Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. | Frierson HF Jr et al |
| 16039883 | 2005 | Sox proteins and neural crest development. | Hong CS et al |
| 18504433 | 2008 | Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma. | Liao YL et al |
| 12815626 | 2003 | Expression of Sox transcription factors in the developing mouse pancreas. | Lioubinski O et al |
| 16618720 | 2006 | Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells. | Liu P et al |
| 12185367 | 2002 | Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice. | Lund AH et al |
| 16636670 | 2006 | Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells. | Pramoonjago P et al |
| 16892424 | 2006 | Cardiac outflow tract: a review of some embryogenetic aspects of the conotruncal region of the heart. | Restivo A et al |
| 15184677 | 2004 | Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. | Rhodes DR et al |
| 9174623 | 1997 | Sox-4 facilitates thymocyte differentiation. | Schilham MW et al |
| 15231650 | 2004 | High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas. | Shin MS et al |
| 12185365 | 2002 | New genes involved in cancer identified by retroviral tagging. | Suzuki T et al |
| 18185580 | 2008 | Endogenous human microRNAs that suppress breast cancer metastasis. | Tavazoie SF et al |
| 16306355 | 2005 | The HMG box transcription factor Sox4 contributes to the development of the endocrine pancreas. | Wilson ME et al |
| 15064731 | 2004 | Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization. | Yokota N et al |
| 18577562 | 2008 | Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis. | de Bont JM et al |
| 8404853 | 1993 | Sox-4, an Sry-like HMG box protein, is a transcriptional activator in lymphocytes. | van de Wetering M et al |
Other Information
Locus ID:
NCBI: 6659
MIM: 184430
HGNC: 11200
Ensembl: ENSG00000124766
Variants:
dbSNP: 6659
ClinVar: 6659
TCGA: ENSG00000124766
COSMIC: SOX4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000124766 | ENST00000244745 | Q06945 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37633471 | 2024 | Cancer-associated fibroblasts drive early pancreatic cancer cell invasion via the SOX4/MMP11 signalling axis. | 1 |
| 37939881 | 2024 | CircHDAC9 regulates myocardial ischemia-reperfusion injury via miR-671-5p/SOX4 signaling axis. | 0 |
| 38227121 | 2024 | SOX4 reversibly induces phenotypic changes by suppressing the epithelial marker genes in human keratinocytes. | 0 |
| 38240850 | 2024 | SOX4/HDAC2 Axis Enhances Cell Survivability and Reduces Apoptosis by Activating AKT/MAPK Signaling in Colorectal Cancer. | 0 |
| 38447391 | 2024 | SOX4 regulates proliferation and apoptosis of human ovarian granulosa-like tumor cell line KGN through the Hippo pathway. | 0 |
| 38650133 | 2024 | circ_JMJD1C expedites breast cancer progression by regulating miR-182-5p/JMJD1C/SOX4 axis. | 0 |
| 38678622 | 2024 | Biological functions of PCAT-1/ SOX4 in cell proliferation and invasion of breast cancer. | 0 |
| 38705228 | 2024 | SOX4 induces cytoskeleton remodeling and promotes cell motility via N-wasp/ARP2/3 pathway in colorectal cancer cells. | 0 |
| 38745044 | 2024 | ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p. | 0 |
| 38751373 | 2024 | LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis. | 1 |
| 38842772 | 2024 | Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis. | 0 |
| 38943117 | 2024 | Deciphering the SOX4/MAPK1 regulatory axis: a phosphoproteomic insight into IQGAP1 phosphorylation and pancreatic Cancer progression. | 0 |
| 37633471 | 2024 | Cancer-associated fibroblasts drive early pancreatic cancer cell invasion via the SOX4/MMP11 signalling axis. | 1 |
| 37939881 | 2024 | CircHDAC9 regulates myocardial ischemia-reperfusion injury via miR-671-5p/SOX4 signaling axis. | 0 |
| 38227121 | 2024 | SOX4 reversibly induces phenotypic changes by suppressing the epithelial marker genes in human keratinocytes. | 0 |
Citation
David L Satinover ; Chris A Moskaluk
SOX4 (SRY (sex determining region Y)-box 4)
Atlas Genet Cytogenet Oncol Haematol. 2009-01-01
Online version: http://atlasgeneticsoncology.org/gene/42358/sox4
