Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance

Mehta, Gaurav; Khanna, Pooja; Gatza, Michael L.

doi:10.1007/s10911-019-09430-6

Cited by 32 publications

(30 citation statements)

References 180 publications

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“…Stem cells and progenitors may serve as a cell of origin for breast cancers. Many SOX (SRY-related HMG-box) transcription factors are expressed in the postnatal breast and some have been shown to control normal and/or CSCs ( Domenici et al, 2019 ; Kogata et al, 2018 ; Mehta et al, 2019 ). SOX11 is a unique transcription factor, since it does not appear to be expressed in normal mammary epithelial cells after birth in either mouse or human and therefore is well-poised to reactivate developmental pathways when expressed in breast cancers ( Oliemuller et al, 2017 ; Tsang et al, 2020 ; Wansbury et al, 2011 ; Zvelebil et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

Oliemuller

Newman

Tsang

et al. 2020

eLife

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SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show that SOX11 confers distinct features to ER-negative DCIS.com breast cancer cells, leading to populations enriched with highly plastic hybrid epithelial/mesenchymal cells, which display invasive features and alterations in metastatic tropism when xenografted into mice. We found that SOX11+DCIS tumour cells metastasize to brain and bone at greater frequency and to lungs at lower frequency compared to cells with lower SOX11 levels. High levels of SOX11 leads to the expression of markers associated with mesenchymal state and embryonic cellular phenotypes. Our results suggest that SOX11 may be a potential biomarker for breast tumours with elevated risk of developing metastases and may require more aggressive therapies.

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Section: Discussionmentioning

confidence: 99%

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

Oliemuller

Newman

Tsang

et al. 2020

eLife

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“…SOX2 expression changes in several types of tumors with varying degrees of differentiation, consistent with its function in maintaining the properties of stem cells in embryonal cells. Several studies showed that this gene plays an important role in forming the undifferentiated stem cell phenotype characteristics associated with basal-like breast carcinoma subtype [11]. Recent studies have shown that SOX2 is overexpressed in early breast carcinoma and has a positive correlation with tumor size [10].…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that SOX2 activation plays an important role in the development of malignancy [10]. Increased SOX2 expression in breast carcinoma also induces epithelial-mesenchymal transitions (EMT) by activating the Wnt/β-catenin pathway which will increase the potency of tumor metastasis [11].…”

Section: Introductionmentioning

confidence: 99%

Correlation of CD133 and SOX2 Expression with Regional Lymph Nodes Metastatic Status in Invasive Breast Carcinoma of No Special Type

Fauziah

Sutrisno

Mastutik

2021

Indonesian Journal of Cancer

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Background: CD133 overexpression can increase cell proliferation, migration, and epithelialmesenchymal transition that promotes metastasis. CD133 expression is induced by hypoxiainduced factor (HIF) which requires SOX2 binding in the promoter region. SOX2 is an embryonal transcription factor that plays a role in the development of malignancy. The study aimed to analyze the expression of CD133 and SOX2 with regional lymph nodes (LN) metastatic status in invasive breast carcinoma of no special type (NST). Methods: The study was a cross-sectional design. Forty-five samples were retrieved from pathology archives in Dr. Soetomo Hospital from January to December 2018. Samples were divided into 2 groups, with and without regional LN metastasis. Immunohistochemistry with CD133 and SOX2 was applied to all samples. CD133 expression was assessed by immunoreactive score, and SOX2 expression was assessed by the percentage of tumor positive cells.Results: There was no significant difference in CD 133 expression between invasive breast carcinoma of NST with and without regional LN metastases (P = .990). A positive correlation was found in SOX2 expression between breast carcinoma with and without regional LN metastasis (P = .000; rs = .518). There was no correlation between CD133 and SOX2 expression (P = .082), which means that the high expression of CD133 did not affect SOX2 expression.Conclusions: CD133 expression was not significantly different in breast carcinoma with and without LN metastasis. The high expression of SOX2 was found significantly correlated with regional LN metastasis. SOX2 expression may become a potential prognostic marker in invasive breast carcinoma of NST. regional LN metastasis

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“…These confirmed EMT associated events occurred in a similar pattern when compared with global gene expression in the early postnatal pig mammary model. EMT-related transcription factors implicated in human breast cancer were identified in our model including CDH1, TWIST, TEAD, SNAI, VEGF, and SOX [28][29][30][31][32][33][34]. The two genes with highest levels of upregulation in later time points include PRRX1 and TEAD1.…”

Section: Discussionmentioning

confidence: 99%

Methodology to analyze gene expression patterns of early mammary development in pig models

et al. 2020

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In mammary gland development, normal stem cell activity occurs in the embryonic stage and postnatally. Research supports that certain breast cancers contain a small sub-population of cells that mimic stem-like activity. It is believed stem cell activation in the mutated mature human mammary tissue is what drives quiescent epithelial cells to convert to mesenchymal states initiating migration, invasion, and metastasis in breast cancer. The goal of the work reported herein was to investigate early mammary development gene expression in the postnatal pig using fine needle biopsy methods in order to establish a reliable model for human breast cancer detection. Tissue samples were collected from pig mammary glands beginning at Day 11 of age through Day 39 in order to capture early postnatal-growth gene expression. Based on the initial clustering analysis, two distinct clusters of gene expression profiles occurred before and after Day 25 of mammary development. Gene set enrichment analysis (GSEA) ontology indicated the cellular processes that changed after Day 25, and many of these processes were implicated in epithelial-mesenchymal transition (EMT) signaling events. Gene expression in the postnatal pig was compared with the Epithelial-Mesenchymal Transition gene database (dbEMT) confirming the presence of EMT activity in this early developmental program. Information from this study will provide insight into early postnatal mammary gland development. In addition, mechanisms exploited by mutated mammary epithelial cells leading to cancer initiation and growth may be detected considering that mutated mammary epithelial cells can reactivate early developmental signals.

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Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance

Cited by 32 publications

References 180 publications

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

Correlation of CD133 and SOX2 Expression with Regional Lymph Nodes Metastatic Status in Invasive Breast Carcinoma of No Special Type

Methodology to analyze gene expression patterns of early mammary development in pig models

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