Abstract
Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres) of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1) and cancer stem cell markers (ABCG2, CD44 and ALDH1) genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7). Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Aldehyde Dehydrogenase 1 Family
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Epithelial-Mesenchymal Transition / genetics
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Gene Expression Regulation, Neoplastic*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Hyaluronan Receptors / genetics
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Hyaluronan Receptors / metabolism
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Nanog Homeobox Protein
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Octamer Transcription Factor-3 / genetics
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Octamer Transcription Factor-3 / metabolism
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Organ Specificity
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Phenotype
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Polycomb Repressive Complex 1 / genetics
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Polycomb Repressive Complex 1 / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Retinal Dehydrogenase / genetics
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Retinal Dehydrogenase / metabolism
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SOXB1 Transcription Factors / genetics
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SOXB1 Transcription Factors / metabolism
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Signal Transduction
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Spheroids, Cellular / metabolism*
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Spheroids, Cellular / pathology
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Telomerase / genetics
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Telomerase / metabolism
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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BMI1 protein, human
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Biomarkers, Tumor
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CD44 protein, human
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CTCFL protein, human
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DNA-Binding Proteins
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Homeodomain Proteins
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Hyaluronan Receptors
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Isoenzymes
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NANOG protein, human
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Nanog Homeobox Protein
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Neoplasm Proteins
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Octamer Transcription Factor-3
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POU5F1 protein, human
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RNA, Small Interfering
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SOX2 protein, human
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SOXB1 Transcription Factors
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Aldehyde Dehydrogenase 1 Family
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ALDH1A1 protein, human
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Retinal Dehydrogenase
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Polycomb Repressive Complex 1
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TERT protein, human
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Telomerase
Grants and funding
Financial support was given by the Swiss National Science Foundation (31003A-113505) and Emma Muschamp Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. One of the authors (JB) is employed by a molecular pathology laboratory (Biopath Lab). Biopath Lab provided support in the form of salaries, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.