Signal transducers and activators of transcription 3 activation is involved in nuclear accumulation of β-catenin in colorectal cancer

Mayumi Kawada, Hiroshi Seno, Yoshito Uenoyama, Tateo Sawabu, Naoki Kanda, Hirokazu Fukui, Yasuyuki Shimahara, Tsutomu Chiba

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    Abstract

    Nuclear accumulation of β-catenin is a key event for the development of colorectal cancer. Little is known, however, about the mechanisms underlying translocation of β-catenin from the cytoplasm or the membrane to the nucleus. The present study examined whether signal transducers and activators of transcription 3 (STAT3) activation is involved in the nuclear accumulation of β-catenin in colorectal cancer cells. Of the 90 primary colorectal cancer tissues, 40 (44.4%) were positive for nuclear staining of p-STAT3 and 63 (70.0%) were positive for nuclear staining of β-catenin. The nuclear staining of both p-STAT3 and β-catenin were observed predominantly in the periphery of the cancer tissues. Importantly, of the 40 tumors with p-STAT3 nuclear staining, 37 (92.5%) were also positive for nuclear β-catenin staining and there was a significant correlation between p-STAT3 and β-catenin nuclear staining (P < 0.01). Coexpression of nuclear p-STAT3 and β-catenin was associated with lower patient survival (P < 0.01). In an in vitro study using a human colon cancer cell line, SW480, inhibition of STAT3 by dominant negative STAT3 or the Janus kinase inhibitor, AG490, induced translocation of β-catenin from the nucleus to the cytoplasm or membrane. Luciferase assays revealed that STAT3 inhibition resulted in significant suppression of β-catenin/T-cell factor transcription in association with significant inhibition of cell proliferation (P < 0.05). These findings suggest that in colorectal cancer, STAT3 activation is involved in the nuclear accumulation of β-catenin, resulting in poor patient survival.

    Original languageEnglish (US)
    Pages (from-to)2913-2917
    Number of pages5
    JournalCancer research
    Volume66
    Issue number6
    DOIs
    StatePublished - Mar 15 2006

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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