GALNT2 enhances migration and invasion of oral squamous cell carcinoma by regulating EGFR glycosylation and activity
Journal
Oral Oncology
Journal Volume
50
Journal Issue
5
Pages
478-484
Date Issued
2014
Author(s)
Abstract
Objectives Oral squamous cell carcinoma (OSCC) is one of the leading cancers worldwide. Aberrant glycosylation affects many cellular properties in cancers, including OSCC. This study aimed to explore the role of N-acetylgalactosaminyltransferase 2 (GALNT2) in OSCC. Materials and methods Immunohistochemistry was performed to study the expression of GALNT2 in an OSCC tissue microarray. Effects of GALNT2 overexpression and knockdown on cell migration and invasion were analyzed in SAS cells by transwell migration assay and matrigel invasion assay, respectively. The Vicia villosa agglutinin (VVA) pull down assay was conducted to detect changes in O-glycans on acceptor substrates of GALNT2. Cell signaling was analyzed by Western blotting. Results GALNT2 was overexpressed in 73% (35/48) of OSCC tissues. Moreover, GALNT2 expression was localized in the invasive front and increased in high grade OSCC. GALNT2 overexpression enhanced migration and invasion of SAS cells triggered by fetal bovine serum (FBS) and epidermal growth factor (EGF). In contrast, GALNT2 knockdown inhibited SAS cell migration and invasion. Furthermore, GALNT2 overexpression enhanced VVA binding to epidermal growth factor receptor (EGFR) and EGF-induced phosphorylation of EGFR and AKT. Conversely, GALNT2 knockdown decreased VVA binding and suppressed activity of EGFR and AKT. Conclusion GALNT2 is frequently overexpressed in OSCC, especially in the carcinoma cells at the invasive front. GALNT2 overexpression enhances the invasive potential of OSCC cells via modifying O-glycosylation and activity of EGFR. These findings suggest that GALNT2 plays an important role in the invasive behavior of OSCC and that targeting GALNT2 could be a promising approach for OSCC therapy. ? 2014 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
agglutinin; epidermal growth factor; epidermal growth factor receptor; matrigel; n acetylgalactosaminyltransferase; n acetylgalactosaminyltransferase 2; protein kinase B; unclassified drug; epidermal growth factor receptor; n acetylgalactosaminyltransferase; polypeptide N-acetylgalactosaminyltransferase; primer DNA; small interfering RNA; article; cancer cell culture; cancer tissue; carcinoma cell; cell invasion assay; cell migration; cell migration assay; controlled study; enzyme activity; enzyme glycosylation; enzyme phosphorylation; fetal bovine serum; gene overexpression; gene silencing; human; human cell; human cell culture; human tissue; immunoassay; immunohistochemistry; intracellular signaling; matrigel invasion assay; mouth squamous cell carcinoma; priority journal; protein glycosylation; protein localization; regulatory mechanism; serum; tissue microarray; transwell migration assay; tumor invasion; Vicia villosa agglutinin pulldown assay; Western blotting; genetics; glycosylation; metabolism; metastasis; mouth tumor; nucleotide sequence; pathology; physiology; real time polymerase chain reaction; squamous cell carcinoma; tumor cell line; Base Sequence; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Primers; Glycosylation; Humans; Mouth Neoplasms; N-Acetylgalactosaminyltransferases; Neoplasm Invasiveness; Neoplasm Metastasis; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor; RNA, Small Interfering
Publisher
Elsevier Ltd
Type
journal article