C1GALT1 overexpression promotes the invasive behavior of colon cancer cells through modifying o-glycosylation of FGFR2
Journal
Oncotarget
Journal Volume
5
Journal Issue
8
Pages
2096-2106
Date Issued
2014
Author(s)
Lin Y.-C.
Huang M.-J.
Abstract
Core 1 β1,3-galactosyltransferase (C1GALT1) transfers galactose (Gal) to N-acetylgalactosamine (GalNAc) to form Galβ1,3GalNAc (T antigen). Aberrant O-glycans, such as T antigen, are commonly found in colorectal cancer. However, the role of C1GALT1 in colorectal cancer remains unclear. Here we showed that C1GALT1 was frequently overexpressed in colorectal tumors and is associated with poor survival. C1GALT1 overexpression promoted cell survival, migration, invasion, and sphere formation as well as tumor growth and metastasis of colon cancer cells. Conversely, knockdown of C1GALT1 with small interference (si) RNA was sufficient to suppress these malignant phenotypes in vitro and in vivo. Moreover, we are the first to show that fibroblast growth factor receptor (FGFR) 2 carried O-glycans in colon cancer cells. Mechanistic investigations showed that C1GALT1 modified the O-glycans on FGFR2 and enhanced bFGF-triggered activation of FGFR2 as well as increased bFGFmediated malignant phenotypes. In addition, BGJ398, a selective inhibitor of FGFR, blocked the effects of C1GALT1. These findings suggest that C1GALT1 overexpression modifies O-glycans on FGFR2 and enhances its phosphorylation to promote the invasive behavior and cancer stem-like property in colon cancer cells, indicating a critical role of O-glycosylation in the pathogenesis of colorectal cancer.
SDGs
Other Subjects
core 1 beta 1,3 galactosyltransferase; fibroblast growth factor receptor 2; galactosyltransferase; small interfering RNA; unclassified drug; C1GALT1 protein, human; FGFR2 protein, human; fibroblast growth factor receptor 2; galactosyltransferase; polysaccharide; animal cell; animal experiment; animal model; animal tissue; article; cancer survival; cell invasion; cell migration; cell survival; colon cancer; controlled study; enzyme activation; enzyme activity; enzyme modification; female; human; human cell; human tissue; in vitro study; in vivo study; mouse; nonhuman; pathogenesis; phenotype; protein expression; protein glycosylation; signal transduction; tumor growth; tumor invasion; adenocarcinoma; animal; cell culture; cell motion; colon tumor; flow cytometry; genetic transfection; glycosylation; immunohistochemistry; immunoprecipitation; Kaplan Meier method; metabolism; mortality; nonobese diabetic mouse; pathology; phosphorylation; real time polymerase chain reaction; reverse transcription polymerase chain reaction; SCID mouse; upregulation; Western blotting; xenograft; Adenocarcinoma; Animals; Blotting, Western; Cell Movement; Cells, Cultured; Colonic Neoplasms; Flow Cytometry; Galactosyltransferases; Glycosylation; Heterografts; Humans; Immunohistochemistry; Immunoprecipitation; Kaplan-Meier Estimate; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Invasiveness; Phosphorylation; Polysaccharides; Real-Time Polymerase Chain Reaction; Receptor, Fibroblast Growth Factor, Type 2; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Up-Regulation
Publisher
Impact Journals LLC
Type
journal article