Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells

Issei Ezawa, Yuichiro Sawai, Tatsuya Kawase, Atsushi Okabe, Shuichi Tsutsumi, Hitoshi Ichikawa, Yuka Kobayashi, Fumio Tashiro, Hideo Namiki, Tadashi Kondo, Kentaro Senba, Hiroyuki Aburatani, Yoichi Taya, Hitoshi Nakagama, Rieko Ohki

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    14 Citations (Scopus)

    Abstract

    The tumor suppressor p53 functions by inducing the transcription of a collection of target genes. We previously attempted to identify p53 target genes by microarray expression and ChIP-sequencing analyses. In this study, we describe a novel p53 target gene, FUCA1, which encodes a fucosidase. Although fucosidase, α-l-1 (FUCA1) has been reported to be a lysosomal protein, we detected it outside of lysosomes and observed that its activity is highest at physiological pH. As there is a reported association between fucosylation and tumorigenesis, we investigated the potential role of FUCA1 in cancer. We found that overexpression of FUCA1, but not a mutant defective in enzyme activity, suppressed the growth of cancer cells and induced cell death. Furthermore, we showed that FUCA1 reduced fucosylation and activation of epidermal growth factor receptor, and concomitantly suppressed epidermal growth factor signaling pathways. FUCA1 loss-of-function mutations are found in several cancers, its expression is reduced in cancers of the large intestine, and low FUCA1 expression is associated with poorer prognosis in several cancers. These results show that protein defucosylation mediated by FUCA1 is involved in tumor suppression.

    Original languageEnglish
    Pages (from-to)734-745
    Number of pages12
    JournalCancer Science
    Volume107
    Issue number6
    DOIs
    Publication statusPublished - 2016 Jun 1

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    Keywords

    • EGFR
    • FUCA1
    • fucosidase
    • fucosylation
    • p53

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Ezawa, I., Sawai, Y., Kawase, T., Okabe, A., Tsutsumi, S., Ichikawa, H., Kobayashi, Y., Tashiro, F., Namiki, H., Kondo, T., Senba, K., Aburatani, H., Taya, Y., Nakagama, H., & Ohki, R. (2016). Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells. Cancer Science, 107(6), 734-745. https://doi.org/10.1111/cas.12933