Sox2: A possible driver of the basal-like phenotype in sporadic breast cancer

Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Modern Pathology (Impact Factor: 6.19). 04/2007; 20(4):474-81. DOI: 10.1038/modpathol.3800760
Source: PubMed


Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2+ tumours, P<0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P=0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P=0.022, 0.005 and <0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics.

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Available from: Yolanda Rodríguez-Gil, Aug 14, 2014
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    • "Differential expression of SOX2 is reported in human cancers [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], including breast cancer from cancer patients and breast cancer cell lines [10], [13], [14], [19], [20]. SOX2 expression has been observed in 43% of basal cell-like breast carcinomas and has been found to be strongly correlated with CK5/6, EGFR, and vimentin immunoreactivity, and to be inversely associated with estrogen and progesterone receptor status, suggesting that SOX2 plays a role in conferring a less differentiated phenotype in these tumors [21], [22]. Other groups have reported SOX2 expression in a variety of early stage postmenopausal breast carcinomas and lymph nodes metastases, suggesting that SOX2 may play an early role in breast carcinogenesis and that high expression may promote metastatic potential [14]. "
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    ABSTRACT: The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT). Here, we show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "The transcription factor sex determining region Y-box 2 (SOX2) is well known to be one of the essential factors for inducing and maintaining the biological nature of stem cells (stemness), namely self-renewal and pluripotency as seen in adult neural progenitor cells (NPCs) [1]. On the other hand, SOX2 is expressed in a variety of cancers such as gastric cancer [2], small cell lung cancer [3], melanoma [4], esophangeal squamous cell carcinoma [5] and breast cancer [6], and may be involved in maintaining cancer stem cells (CSCs) which can self-renew, and have pluripotent and tumorigenic ability. However, biological roles of SOX2 in cancer cells remain undetermined. "
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    ABSTRACT: Sex-determining region Y-box 2 (SOX2) is well known as one of the "stemness" factors and is often expressed in cancers including breast cancer. In this study, we developed a reporter system using fluorescent protein driven by the promoter for SOX2 gene to detect and isolate living SOX2-positive cells. Using this system, we determined that SOX2 promoter activities were well correlated with SOX2 mRNA expression levels in 5 breast cancer cell lines, and that the cell population with positive SOX2 promoter activity (pSp-T(+)) isolated from one of the 5 cell lines, MCF-7 cells, showed a high SOX2 protein expression and high sphere-forming activity compared with very low promoter activity (pSp-T(low/-)). The pSp-T(+) population expressed higher mRNA levels of several stemness-related genes such as CD44, ABCB1, NANOG and TWIST1 than the pSp-T(low/-) population whereas the two populations expressed CD24 at similar levels. These results suggest that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show expression profiles different from those of CSC-marker genes previously recognized in human breast cancers.
    Full-text · Article · Jun 2013 · Biochemical and Biophysical Research Communications
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    • "Although the oncogenic potential of stem cell factors, such as Sox2, has been hypothesized to be based on the “stemness” similarity between stem cells and cancer cells, Sox2’s function in cancer cells is not clearly understood. Furthermore, recent studies have shown that the Sox2 protein level strongly corresponds with less differentiated basal cell-like breast carcinomas [22], and the Sox2 protein is frequently found to be down-regulated in gastric carcinomas [23]. These types of studies have caused more controversy regarding the normal function and oncogenic potential of stem cell factors. "
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    ABSTRACT: Autophagy is a critical cellular process required for maintaining cellular homeostasis in health and disease states, but the molecular mechanisms and impact of autophagy on cancer is not fully understood. Here, we found that Sox2, a key transcription factor in the regulation of the "stemness" of embryonic stem cells and induced-pluripotent stem cells, strongly induced autophagic phenomena, including intracellular vacuole formation and lysosomal activation in colon cancer cells. The activation occurred through Sox2-mediated gene expression and resulted in the inhibition of cell proliferation and anchorage-independent colony growth and tumor growth Further, we found that Sox2-induced-autophagy enhanced cellular senescence by up-regulating tumor suppressors or senescence factors, including p16, p21 and phosphorylated p53 (Ser15). Notably, knockdown of in -expressing colon cancer cells restored cancer cell properties. Taken together, our results demonstrated that regulation of autophagy mediated by Sox2 is a mechanism-driven novel strategy to treat human colon cancers.
    Full-text · Article · Feb 2013 · PLoS ONE
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