The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression

Abstract

Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer.

SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours

“…In breast cancer, we observed that 17% of breast carcinomas showed SOX11 positivity and the six SOX11‐positive cases were all ER − /PR − /HER2 +/− (Table ). Our finding is consistent with a previous report that SOX11 is expressed in basal‐like and HER2‐enriched subtypes . In addition, SOX11 is proposed to be oncogenic, as it promotes the proliferation and invasion of breast cancer cells and is associated with poor survival .…”

“…Our finding is consistent with a previous report that SOX11 is expressed in basal-like and HER2-enriched subtypes. 16 In addition, SOX11 is proposed to be oncogenic, as it promotes the proliferation and invasion of breast cancer cells and is associated with poor survival. 16 For ovarian serous cancer, a previous report has shown SOX11 expression in different kinds of ovarian cancers including serous, mucinous and endometrial carcinoma and, proposed that its expression was associated with improved survival in high-grade ovarian cancer.…”

“…16 In addition, SOX11 is proposed to be oncogenic, as it promotes the proliferation and invasion of breast cancer cells and is associated with poor survival. 16 For ovarian serous cancer, a previous report has shown SOX11 expression in different kinds of ovarian cancers including serous, mucinous and endometrial carcinoma and, proposed that its expression was associated with improved survival in high-grade ovarian cancer. 17 However, we found that scattered nuclear staining of SOX11 was only identified in 20% of high-grade serous carcinomas, but not in low-grade serous carcinoma, mucinous or endometrial carcinoma ( Table 2).…”

“…Additionally, there are a few reports demonstrating SOX11 expression in mRNA and proteins of some malignant epithelial tumours. [14][15][16][17][18] However, the expression and significance of SOX11 using immunohistochemistry (IHC) analysis in different tumour types has not been thoroughly investigated.…”

Ferramenta de bioinformática para integrar e compreender as mudanças epigenômicas e genômicas aberrantes associadas com câncer: métodos, desenvolvimento e análise

“…It is important to note that we expect these analyses to have increased statistical power over Unsupervised analyses, as illustrated above in Figure 17. One useful output plot is the comprehensive heatmap, which illustrates the identification of inverse correlated probe-gene pairs (Figure 25) TF; this correlation between basal-like and SOX11 was recently described by (SHEPHERD et al, 2016) and SOX9 was described by (GONG et al, 2015). Most interestingly, we found KLF5 to be a consistently predicted MR for the Basal-like breast subtype.…”