Open AccessNovel p53 target gene FUCA 1 encodes a fucosidase and regulates growth and survival of cancer cells
Author(s) -
Ezawa Issei,
Sawai Yuichiro,
Kawase Tatsuya,
Okabe Atsushi,
Tsutsumi Shuichi,
Ichikawa Hitoshi,
Kobayashi Yuka,
Tashiro Fumio,
Namiki Hideo,
Kondo Tadashi,
Semba Kentaro,
Aburatani Hiroyuki,
Taya Yoichi,
Nakagama Hitoshi,
Ohki Rieko
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12933
Subject(s) - biology , carcinogenesis , cancer research , transcription factor , fucosylation , gene , cancer , tumor suppressor gene , cancer cell , cell growth , microbiology and biotechnology , programmed cell death , genetics , apoptosis , glycoprotein , glycan
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 Ch IP ‐sequencing analyses. In this study, we describe a novel p53 target gene, FUCA 1 , which encodes a fucosidase. Although fucosidase, α‐ l ‐1 ( FUCA 1) 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 FUCA 1 in cancer. We found that overexpression of FUCA 1, but not a mutant defective in enzyme activity, suppressed the growth of cancer cells and induced cell death. Furthermore, we showed that FUCA 1 reduced fucosylation and activation of epidermal growth factor receptor, and concomitantly suppressed epidermal growth factor signaling pathways. FUCA 1 loss‐of‐function mutations are found in several cancers, its expression is reduced in cancers of the large intestine, and low FUCA 1 expression is associated with poorer prognosis in several cancers. These results show that protein defucosylation mediated by FUCA 1 is involved in tumor suppression.