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Keywords {🔍}

cells, cancer, muc, ston, expression, ovarian, pubmed, article, google, scholar, fig, analysis, stem, caov, cas, cell, usa, dna, methylation, data, dnmt, patients, additional, file, experiments, knockdown, stemlike, levels, spheroids, transfected, central, detected, overexpression, nanog, protein, level, cmyc, cultured, properties, survival, control, cdcd, shown, parental, culture, days, study, ocscs, low, figure,

Topics {✒️}

pi3k/akt/c-myc axis promotes wnt/beta-catenin signaling pathway 5-aza-2′-deoxycytidine-induced genome rearrangements significantly reduced cd44+cd24−phenotypes stem cell related-markers ha-tagged human muc1 dnmt1/muc1-mediated epigenetic mechanisms dnmt1-mediated epigenetic modification muc1-positive cell line platinum-resistant ovarian cancer lc-ms/ms analysis lc-ms/ms data usp7-mediated dnmt1 stabilization 10 μl/ml b27 additive cd44+cd24− cell population article download pdf cancer stem cell paired-end clean reads cpg dinucleotide-rich regions sphere-forming ability assay epithelial mesenchymal transition epithelial–mesenchymal transition epithelial-mesenchymal transition sphere-forming ability assays csc subpopulation-induced tumorigenicity ovarian cancer stem csc-related markers nanog ston2 overexpression-induced reduction ocsc-specific gene expressions aza dosage-dependent increase cancer stem cells ston2 knockdown-induced muc1 emt-related key factors ston2 knockdown-induced reduction ston2 modulates stem csc-related proteins showed ocsc-enriched population displays epithelial ovarian cancer paraffin-embedded tissue samples ston2-dnmt1/muc1 pathway 5 μg/ml puromycin serum muc1-specific antibodies emt-related protein expression ms/ms spectra pluripotent stem cells ferritin heavy chain privacy choices/manage cookies ston2 negatively modulates caov3 cell line 3ao cell line

Questions {❓}

• Ovarian cancer stem cells: still an elusive entity?

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         headline:STON2 negatively modulates stem-like properties in ovarian cancer cells via DNMT1/MUC1 pathway
         description:Cancer stem cells (CSCs) possess abilities of self-renewal and differentiation, have oncogenic potential and are regarded to be the source of cancer recurrence. However, the mechanism by which CSCs maintain their stemness remains largely unclear. In this study, the cell line-derived ovarian CSCs (OCSCs), 3AO and Caov3, were enriched in serum-free medium (SFM). Differentially expressed proteins were compared between the OCSC subpopulation and parental cells using liquid chromatography (LC)-mass spectrometry (MS)/MS label-free quantitative proteomics. Sphere-forming ability assays, flow cytometry, quantitative real-time polymerase chain reaction (qPCR), western blotting, and in vivo xenograft experiments were performed to evaluate stemness. RNA-sequencing (RNA-seq) and pyrosequencing were used to reveal the mechanism by which STON2 negatively modulates the stem-like properties of ovarian cancer cells. Among the 74 most differentially expressed proteins, stonin 2 (STON2) was confirmed to be down-regulated in the OCSC subpopulation. We show that STON2 negatively modulates the stem-like properties of ovarian cancer cells, which are characterized by sphere formation, a CD44+CD24− ratio, and by CSC- and epithelial mesenchymal transition (EMT)-related markers. STON2 knockdown also accelerated tumorigenesis in NOD/SCID mice. Further investigation revealed a downstream target, mucin 1 (MUC1), as up-regulated upon the down regulation of STON2. A decrease in both DNA methyltransferase 1 (DNMT1) expression and methylation in the promoter region of MUC1 was associated with subsequently elevated MUC1 expression, as detected in STON2 knockdown in 3AO and Caov3 cells. Direct DNMT1 knockdown simultaneously elevated MUC1 expression. The functional significance of this STON2-DNMT1/MUC1 pathway is supported by the observation that STON2 overexpression suppresses MUC1-induced sphere formation of OCSCs. The paired expression of STON2 and MUC1 in ovarian cancer specimens was also detected revealing the prognostic value of STON2 expression to be highly dependent on MUC1 expression. Our results imply that STON2 may negatively regulate stemness in ovarian cancer cells via DNMT1-MUC1 mediated epigenetic modification. STON2 is therefore involved in OCSC biology and may represent a therapeutic target for innovative treatments aimed at ovarian cancer eradication.
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            Ovarian cancer
            Cancer stem cell
            STON2
            MUC1
            DNMT1
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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      headline:STON2 negatively modulates stem-like properties in ovarian cancer cells via DNMT1/MUC1 pathway
      description:Cancer stem cells (CSCs) possess abilities of self-renewal and differentiation, have oncogenic potential and are regarded to be the source of cancer recurrence. However, the mechanism by which CSCs maintain their stemness remains largely unclear. In this study, the cell line-derived ovarian CSCs (OCSCs), 3AO and Caov3, were enriched in serum-free medium (SFM). Differentially expressed proteins were compared between the OCSC subpopulation and parental cells using liquid chromatography (LC)-mass spectrometry (MS)/MS label-free quantitative proteomics. Sphere-forming ability assays, flow cytometry, quantitative real-time polymerase chain reaction (qPCR), western blotting, and in vivo xenograft experiments were performed to evaluate stemness. RNA-sequencing (RNA-seq) and pyrosequencing were used to reveal the mechanism by which STON2 negatively modulates the stem-like properties of ovarian cancer cells. Among the 74 most differentially expressed proteins, stonin 2 (STON2) was confirmed to be down-regulated in the OCSC subpopulation. We show that STON2 negatively modulates the stem-like properties of ovarian cancer cells, which are characterized by sphere formation, a CD44+CD24− ratio, and by CSC- and epithelial mesenchymal transition (EMT)-related markers. STON2 knockdown also accelerated tumorigenesis in NOD/SCID mice. Further investigation revealed a downstream target, mucin 1 (MUC1), as up-regulated upon the down regulation of STON2. A decrease in both DNA methyltransferase 1 (DNMT1) expression and methylation in the promoter region of MUC1 was associated with subsequently elevated MUC1 expression, as detected in STON2 knockdown in 3AO and Caov3 cells. Direct DNMT1 knockdown simultaneously elevated MUC1 expression. The functional significance of this STON2-DNMT1/MUC1 pathway is supported by the observation that STON2 overexpression suppresses MUC1-induced sphere formation of OCSCs. The paired expression of STON2 and MUC1 in ovarian cancer specimens was also detected revealing the prognostic value of STON2 expression to be highly dependent on MUC1 expression. Our results imply that STON2 may negatively regulate stemness in ovarian cancer cells via DNMT1-MUC1 mediated epigenetic modification. STON2 is therefore involved in OCSC biology and may represent a therapeutic target for innovative treatments aimed at ovarian cancer eradication.
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      dateModified:2018-12-05T00:00:00Z
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         Ovarian cancer
         Cancer stem cell
         STON2
         MUC1
         DNMT1
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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      name:Women’s Reproductive Health Laboratory of Zhejiang Province; Women’s Hospital; School of Medicine, Zhejiang University, Hangzhou, China
      name:Department of Gynecologic Oncology; Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
      name:Women’s Reproductive Health Laboratory of Zhejiang Province; Women’s Hospital; School of Medicine, Zhejiang University, Hangzhou, China
      name:Department of Gynecologic Oncology; Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
      name:Women’s Reproductive Health Laboratory of Zhejiang Province; Women’s Hospital; School of Medicine, Zhejiang University, Hangzhou, China

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