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. 2014 Jun 2;1(5):326-35.
doi: 10.18632/oncoscience.46. eCollection 2014.

SOX15 and other SOX family members are important mediators of tumorigenesis in multiple cancer types

Kelsie L Thu  1 , Daiana D Becker-Santos  1 , Nikolina Radulovich  1 , Larissa A Pikor  1 , Wan L Lam  1 , Ming-Sound Tsao  2
Affiliations

SOX15 and other SOX family members are important mediators of tumorigenesis in multiple cancer types

Kelsie L Thu et al. Oncoscience. .

Abstract

SOX genes are transcription factors with important roles in embryonic development and carcinogenesis. The SOX family of 20 genes is responsible for regulating lineage and tissue specific gene expression patterns, controlling numerous developmental processes including cell differentiation, sex determination, and organogenesis. As is the case with many genes involved in regulating development, SOX genes are frequently deregulated in cancer. In this perspective we provide a brief overview of how SOX proteins can promote or suppress cancer growth. We also present a pan-cancer analysis of aberrant SOX gene expression and highlight potential molecular mechanisms responsible for their disruption in cancer. Our analyses indicate the prominence of SOX deregulation in different cancer types and reveal potential roles for SOX genes not previously described in cancer. Finally, we summarize our recent identification of SOX15 as a candidate tumor suppressor in pancreatic cancer and propose several research avenues to pursue to further delineate the emerging role of SOX15 in development and carcinogenesis.

Keywords: SOX; SOX15; cancer; development; oncogene; tumor suppressor.

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Conflict of interest statement

Conflicts of Interest

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Pan-cancer analysis of SOX gene expression levels
Processed Cancer Genome Atlas (TCGA) SOX family gene expression data for tumor and non-malignant tissues from 11 different cancer types was downloaded from the UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) [92]. The number of tumor samples for each cancer type is indicated in brackets. Gene expression was classified as over- or underexpressed in individual tumors if tumor expression was at least 2-fold more or less than the average expression of available tissue matched non-malignant samples, and the frequency of expression changes across tumors of each type was calculated. Darker coloration indicates a higher frequency of alteration as indicated in the legends below each heatmap, with underexpression depicted on the left in red and overexpression on the right in blue. Genes were considered recurrently, aberrantly expressed within a particular cancer type if they exhibited a 20% or greater frequency in disruption. Cancer types are annotated as follows: BLCA - bladder urothelial carcinoma; BRCA - breast invasive carcinoma; COAD - colon adenocarcinoma; HNSC - head and neck squamous cell carcinoma; KIRC - kidney clear cell carcinoma; LUAD - lung adenocarcinoma; LUSC - lung squamous cell carcinoma; PRAD - prostate adenocarcinoma; STAD - stomach adenocarcinoma; THCA - thyroid carcinoma; UCEC - uterine corpus endometrioid carcinoma.
Figure 2
Figure 2. Involvement of SOX proteins in various developmental pathways that have been associated with tumorigenesis
SOX members are involved in regulating several signaling pathways relevant to tumorigenesis, including the Wnt, Hedgehog, Notch, and Hippo pathways. (A) In the Wnt pathway, SOX proteins can bind β-catenin or TCF/LEF to either promote or suppress Wnt mediated transcriptional activity. (B) In the Hedgehog pathway, SOX proteins act upstream to control the expression of sonic hedgehog (Shh) and downstream through interaction with GLI to promote transcription of pathway target genes. (C) In the Notch and Hippo pathways, SOX proteins bind with other factors to control expression of their transcription factor effectors, HES1 and TEAD2, respectively.
Figure 3
Figure 3. SOX15 expression status in various cancer types
Frequency of SOX15 over- and underexpression in 11 cancer types, illustrating SOX15 is predominantly underexpressed in cancer with the exception of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), in which it is frequently overexpressed. Cancer types are annotated as follows: BLCA - bladder urothelial carcinoma; BRCA - breast invasive carcinoma; COAD - colon adenocarcinoma; HNSC - head and neck squamous cell carcinoma; KIRC - kidney clear cell carcinoma; LUAD - lung adenocarcinoma; LUSC - lung squamous cell carcinoma; PRAD - prostate adenocarcinoma; STAD - stomach adenocarcinoma; THCA - thyroid carcinoma; UCEC - uterine corpus endometrioid carcinoma.
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