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 Semba, Hiroyuki Aburatani, Yoichi Taya, Hitoshi Nakagama and Rieko Ohki
Version of Record online: 16 MAY 2016 | DOI: 10.1111/cas.12933
We show that a p53 target gene, FUCA1, encodes a fucosidase and has a tumor suppressive function. Expression of FUCA1 suppressed the growth of cancer cells and induced cell death in a manner dependent on its enzymatic activity. Furthermore, we showed that expression of FUCA1 reduced the fucosylation and activation of EGFR, and concomitantly suppressed downstream EGF signaling pathways. In addition, we found that loss-of-function mutations in FUCA1 occur in some cancers, as well as reduced expression. Low FUCA1 expression is also associated with poorer prognosis in cancer patients. These results collectively suggest that defucosylation by FUCA1 contributes to tumor suppression, and thus identifies a novel mechanism of tumor suppression that involves FUCA1-mediated protein defucosylation.