title: I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling.
abstract: Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I-branching N-acetylglucosaminyltransferase (GCNT2) 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 GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin-embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2-positive cells were significantly lesser in organ-confined disease than in that with extra-capsular extensions, and GCNT2-negative tumors were associated with significantly better prostate-specific antigen-free survival compared with GCNT2-positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 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, GCNT2 expression is closely associated with invasive potential of PCa.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Jotaro
authors.initials: J
authors.lastname: Mikami
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.|Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tobisawa
authors.affiliation: Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoneyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.|Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.affiliation: Hirosaki University Graduate School of Medicine, Hirosaki, Japan.|Sanford Burnham Prebys Medical Discovery Institute, Tumor Microenvironment and Metastasis Program, NCI-Designated Cancer Center, La Jolla, California, USA.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D018572:Disease-Free Survival; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell migration; I-antigen; I-branching N-acetylglucosaminyltransferase; glycolipid; prostate cancer