Open AccessI‐branching N ‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling
Author(s) -
Mikami Jotaro,
Tobisawa Yuki,
Yoneyama Tohru,
Hatakeyama Shingo,
Mori Kazuyuki,
Hashimoto Yasuhiro,
Koie Takuya,
Ohyama Chikara,
Fukuda Minoru
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.12859
Subject(s) - cancer research , gene knockdown , glycolipid , antigen , integrin , fibronectin , cell , tumor progression , biology , prostate cancer , cell migration , cancer , cell culture , microbiology and biotechnology , chemistry , immunology , biochemistry , genetics
Cell surface carbohydrates are important for cell migration and invasion of prostate cancer ( PC a). Accordingly, the I‐branching N ‐acetylglucosaminyltransferase ( GCNT 2) converts linear i‐antigen to I‐branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT 2 expression and clinicopathological parameters in patients with PC a. Paraffin‐embedded PC a specimens were immunohistochemically tested for GCNT 2 expression, and the roles of GCNT 2 in PC a progression were investigated using cell lines with high GCNT 2 expression and low GCNT 2 expression. GCNT 2‐positive cells were significantly lesser in organ‐confined disease than in that with extra‐capsular extensions, and GCNT 2‐negative tumors were associated with significantly better prostate‐specific antigen‐free survival compared with GCNT 2‐positive tumors. Subsequent functional studies revealed that knockdown of GCNT 2 expression in PC a cell lines significantly inhibited cell migration and invasion. GCNT 2 regulated the expression of cell surface I‐antigen on the O ‐glycan and glycolipid. Moreover, I‐antigen‐bearing glycolipids were subject to α5β1 integrin–fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT 2 expression is closely associated with invasive potential of PC a.