Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells

Anders K. Olsen, Mehmet Coskun, Michael Bzorek, Michael Kristensen, Erik Thomas Danielsen, Steffen Jørgensen, Jørgen Olsen, Ulla Engel, Susanne Holck, Jesper Troelsen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Wnt signalling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signalling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2 bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analysed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activity via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous down-regulation of APC and AXIN2 expression in Caco-2 cells but did not effect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signalling in invasive colon cancer cells possibly promoting cellular migration.
    OriginalsprogEngelsk
    TidsskriftCarcinogenesis
    Vol/bind34
    Udgave nummer6
    Sider (fra-til)1361-1369
    ISSN0143-3334
    DOI
    StatusUdgivet - 2013

    Citer dette

    Olsen, A. K., Coskun, M., Bzorek, M., Kristensen, M., Danielsen, E. T., Jørgensen, S., ... Troelsen, J. (2013). Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis, 34(6), 1361-1369. https://doi.org/10.1093/carcin/bgt037
    Olsen, Anders K. ; Coskun, Mehmet ; Bzorek, Michael ; Kristensen, Michael ; Danielsen, Erik Thomas ; Jørgensen, Steffen ; Olsen, Jørgen ; Engel, Ulla ; Holck, Susanne ; Troelsen, Jesper. / Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. I: Carcinogenesis. 2013 ; Bind 34, Nr. 6. s. 1361-1369.
    @article{1ea8293fcd6c45a4be6f7382e0b61add,
    title = "Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells",
    abstract = "Wnt signalling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signalling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2 bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analysed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activity via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous down-regulation of APC and AXIN2 expression in Caco-2 cells but did not effect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signalling in invasive colon cancer cells possibly promoting cellular migration.",
    author = "Olsen, {Anders K.} and Mehmet Coskun and Michael Bzorek and Michael Kristensen and Danielsen, {Erik Thomas} and Steffen J{\o}rgensen and J{\o}rgen Olsen and Ulla Engel and Susanne Holck and Jesper Troelsen",
    year = "2013",
    doi = "10.1093/carcin/bgt037",
    language = "English",
    volume = "34",
    pages = "1361--1369",
    journal = "Carcinogenesis",
    issn = "0143-3334",
    publisher = "Oxford University Press",
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    }

    Olsen, AK, Coskun, M, Bzorek, M, Kristensen, M, Danielsen, ET, Jørgensen, S, Olsen, J, Engel, U, Holck, S & Troelsen, J 2013, 'Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells', Carcinogenesis, bind 34, nr. 6, s. 1361-1369. https://doi.org/10.1093/carcin/bgt037

    Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. / Olsen, Anders K.; Coskun, Mehmet; Bzorek, Michael; Kristensen, Michael; Danielsen, Erik Thomas; Jørgensen, Steffen; Olsen, Jørgen; Engel, Ulla; Holck, Susanne; Troelsen, Jesper.

    I: Carcinogenesis, Bind 34, Nr. 6, 2013, s. 1361-1369.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells

    AU - Olsen, Anders K.

    AU - Coskun, Mehmet

    AU - Bzorek, Michael

    AU - Kristensen, Michael

    AU - Danielsen, Erik Thomas

    AU - Jørgensen, Steffen

    AU - Olsen, Jørgen

    AU - Engel, Ulla

    AU - Holck, Susanne

    AU - Troelsen, Jesper

    PY - 2013

    Y1 - 2013

    N2 - Wnt signalling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signalling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2 bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analysed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activity via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous down-regulation of APC and AXIN2 expression in Caco-2 cells but did not effect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signalling in invasive colon cancer cells possibly promoting cellular migration.

    AB - Wnt signalling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signalling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2 bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analysed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activity via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous down-regulation of APC and AXIN2 expression in Caco-2 cells but did not effect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signalling in invasive colon cancer cells possibly promoting cellular migration.

    U2 - 10.1093/carcin/bgt037

    DO - 10.1093/carcin/bgt037

    M3 - Journal article

    VL - 34

    SP - 1361

    EP - 1369

    JO - Carcinogenesis

    JF - Carcinogenesis

    SN - 0143-3334

    IS - 6

    ER -

    Olsen AK, Coskun M, Bzorek M, Kristensen M, Danielsen ET, Jørgensen S et al. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis. 2013;34(6):1361-1369. https://doi.org/10.1093/carcin/bgt037