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.

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

“…GCNT2 is one such glycan‐related gene that is induced upon EMT of cancer cells. Our overexpression and knockdown experiments clearly demonstrate that GCNT2 has cancer‐promoting functions such as enhancing cell motility and invasiveness not only in colon cancer cells (this study) but also in breast cancer cells and prostate cancer cells , and thus GCNT2 promotes tumorigenesis independently of cancer type.…”

GCNT2 induces epithelial‐mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma cells

“…11,12 The I-branching N-acetylglucosaminyltransferase (GCNT2), one of cell surface carbohydrates, can synthesize I-branched polylactosamine chains (I-antigen) by catalysing the transfer of N-acetylglucosamine (GlcNAc) from uridine diphosphate-GlcNAc with a galactose β1-6 linkage of linear lactosamine chains. [14][15][16] For example, GCNT2 is overexpressed in highly metastatic breast cancer cell lines and basal-like breast tumour samples. [14][15][16] For example, GCNT2 is overexpressed in highly metastatic breast cancer cell lines and basal-like breast tumour samples.…”

“…[14][15][16] For example, GCNT2 is overexpressed in highly metastatic breast cancer cell lines and basal-like breast tumour samples. 15 However, the role of GCNT2 in ESCC remains enigmatic yet. Interestingly, knockdown of GCNT2 by its specific small hairpin RNA (shRNA) or inhibition of its glycosyltransferase activity in breast cancer cell lines significantly abrogates the TGF-β-induced EMT, consequently inhibits cell migration and invasion in vitro, and lung metastasis of breast cancer cells in vivo.…”

“…13 It is reported that GCNT2 is implicated in tumour metastasis in several types of human cancers. [14][15][16] For example, GCNT2 is overexpressed in highly metastatic breast cancer cell lines and basal-like breast tumour samples. The expression of GCNT2 is directly regulated by transforming growth factor β (TGF-β)-smad pathway.…”

“…14 In prostate cancer, GCNT2 regulates prostate cancer invasiveness through enhancing α5β1 integrin signalling. 15 However, the role of GCNT2 in ESCC remains enigmatic yet.…”