β-1,4-Galactosyltransferase III suppresses β1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer
Journal
Carcinogenesis
Journal Volume
35
Journal Issue
6
Pages
1258-1266
Date Issued
2014
Author(s)
Chen C.-H.
Wang S.-H.
Liu C.-H.
Wu Y.-L.
Wang W.-J.
Abstract
Metastasis often occurs in colorectal cancer (CRC) patients and is the main difficulty in cancer treatment. The upregulation of poly-N-acetyllactosamine-related glycosylation is found in CRC patients and is associated with progression and metastasis in cancer. β-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for poly-N-acetyllactosamine synthesis, and therefore, we investigated its expression in CRC patients. We found that B4GALT3 negatively correlated with poorly differentiated histology (P < 0.001), advanced stages (P = 0.0052), regional lymph node metastasis (P = 0.0018) and distant metastasis (P = 0.0463) in CRC patients. B4GALT3 overexpression in CRC cells suppressed cell migration, invasion and adhesion, whereas B4GALT3 knockdown enhanced malignant cell phenotypes. The β1 integrin- blocking antibody reversed the B4GALT3-mediated increase in cell invasion. B4GALT3 expression altered glycosylation on the N-glycan of β1 integrin probably through changes in poly- N-acetyllactosamine expression. Furthermore, more activated β1 integrin along with the activation of its downstream signaling transduction were found in B4GALT3 knockdown cells, whereas overexpression of B4GALT3 suppressed the expression of active β1 integrin and inhibited its downstream signaling. Our results suggest that B4GALT3 is negatively associated with CRC metastasis and suppresses cell invasiveness through inhibiting activation of β1 integrin. ? The Author 2014. Published by Oxford University Press. All rights reserved.
SDGs
Other Subjects
beta 1,4 galactosyltransferase III; beta1 integrin; glycosyltransferase; unclassified drug; beta1 integrin; beta4 galactosyltransferase III; beta4-galactosyltransferase III; galactosyltransferase; lectin; adult; advanced cancer; Article; cancer cell; cancer patient; carcinogenesis; cell adhesion; cell invasion; cell migration; colorectal cancer; controlled study; distant metastasis; female; gene silencing; glycosylation; histology; human; human cell; human tissue; lymph node metastasis; major clinical study; male; middle aged; phenotype; priority journal; protein expression; aged; article; cancer grading; cancer staging; cell motion; cell proliferation; colorectal tumor; extracellular matrix; gene expression; genetics; immunohistochemistry; metabolism; metastasis; pathology; phenotype; signal transduction; tumor cell line; tumor invasion; Adult; Aged; Antigens, CD29; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Extracellular Matrix; Female; Galactosyltransferases; Gene Expression; Glycosylation; Humans; Immunohistochemistry; Lectins; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Phenotype; Signal Transduction
Publisher
Oxford University Press
Type
journal article