Beta1,4-N-acetylgalactosaminyltransferase III enhances malignant phenotypes of colon cancer cells.
The enzyme beta1,4-N-acetylgalactosaminyltransferase III (beta4GalNAc-T3) exhibits in vitro activity of synthesizing N,N'-diacetyllactosediamine, GalNAcbeta1,4GlcNAc. Here, we investigate the expression of beta4GalNAc-T3 in primary colon tumors and the effects of its overexpression on HCT116 colon cancer cells. Real-time reverse transcription-PCR showed that the expression of beta4GalNAc-T3 was up-regulated in 72.5% (n = 40) of primary colon tumors compared with their normal counterparts. beta4GalNAc-T3 overexpression resulted in enhanced cell-extracellular matrix adhesion, migration, anchorage-independent cell growth, and invasion of colon cancer cells. Moreover, beta4GalNAc-T3 overexpression increased tumor growth and metastasis and decreased survival of tumor-bearing nude mice. beta4GalNAc-T3 overexpression showed increased tyrosine phosphorylation of focal adhesion kinase and paxillin Y118 as well as increased extracellular signal-regulated kinase phosphorylation. These results suggest that up-regulation of beta4GalNAc-T3 may play a critical role in promoting tumor malignancy and that integrin and mitogen-activated protein kinase signaling pathways could be involved in the underlying mechanism.
Huang
John
J
Department of Surgery, National Taiwan University Hospital, Taiwan.
Liang
Jin-Tung
JT
Huang
Hsiu-Chin
HC
Shen
Tang-Long
TL
Chen
Hsiao-Yu
HY
Lin
Neng-Yu
NY
Che
Mei-Ieng
MI
Lin
Wei-Chou
WC
Huang
Min-Chuan
MC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051419:Paxillin / Q000494:pharmacology; D010641:Phenotype
D000970:Antineoplastic Agents; D051419:Paxillin; C480161:B4GALNT3 protein, human; D017350:N-Acetylgalactosaminyltransferases; D051416:Focal Adhesion Protein-Tyrosine Kinases