ヤマウチ アキラ
  山内 明
   所属   川崎医科大学  医学部 基礎医学 生化学
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 b-1,3-galactosyl-O-glycosyl-glycoprotein b-1,6-N-acetylglucosaminyltransferase 3 increases MCAM stability, which enhances S100A8/A9-mediated cancer motility. Short Title: GCNT3 enhanced S100A8/A9-mediated cancer motility.
掲載誌名 正式名:Oncology Research
略  称:Oncol Res
ISSNコード:09650407/15553906
掲載区分国外
出版社 Cognizant Communication Corporation
巻・号・頁 26(3),431-444頁
著者・共著者 Sumardika WI, Youyi C, Kondo E, Inoue Y, Ruma MIW, Murata H, Kinoshita R, Yamamoto K, Tomida S, Shien K, Satoh H, Yamauchi A, Futami J, Putranto EW, Hibino T, Toyooka S, Nishibori M, Sakaguchi M
発行年月 2017/03
概要 We previously identified novel S100A8/A9 receptors, Extracellular Matrix
Metalloproteinase Inducer (EMMPRIN), Melanoma Cell Adhesion Molecule (MCAM),
Activated Leukocyte Cell Adhesion Molecule (ALCAM) and Neuroplastin (NPTN) !,
that are critically involved in S100A8/A9-mediated cancer metastasis and inflammation
when expressed at high levels. However, little is known about the presence of any
cancer-specific mechanism(s) that modifies these receptors, further inducing
upregulation at protein levels without any transcriptional regulation. Expression levels
of glycosyltransferase-encoding genes were examined by a PCR-based profiling array
followed by confirmation with quantitative real time PCR. Cell migration and invasion
were assessed by a using Boyden chamber. Western blotting was used to examine the
protein level, and the RNA level was examined by Northern blotting.
Immunohistochemistry was used to examine the expression pattern of GCNT3 and
MCAM in melanoma tissue. We found that !-1,3-galactosyl-O-glycosyl-glycoprotein
!-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) is overexpressed in highly
metastatic melanomas. Silencing and functional inhibition of GCNT3 greatly
3
suppressed migration and invasion of melanoma cells, resulting in the loss of
S100A8/A9 responsiveness. Among the novel S100A8/A9 receptors, GCNT3 favorably
glycosylates the MCAM receptor, extending its half-life and leading to further elevation
of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 expression is
positively correlated to MCAM expression in patients with high-grade melanomas.
Collectively, our results showed that GCNT3 is an upstream regulator of MCAM
protein and indicate the possibility of a potential molecular target in melanoma
therapeutics through abrogation of the S100A8/A9-MCAM axis.
DOI https://doi.org/10.3727/096504017X15031557924123
NAID in press
PMID 28923134