Branching N-linked oligosaccharides in breast cancer.
Tumor progression in rodent and human tumors is commonly associated with changes in glycoprotein glycosylation, in particular increased beta 1-6GlcNAc-branching, a regulatory step in expression of polylactosamine and extended-chain Lewis antigens. Loss of the branched oligosaccharides in murine tumor cells either due to somatic mutation, or treatment of the cells with the oligosaccharide processing inhibitor swainsonine, blocks tumor cells invasion in vitro and reduces solid tumor growth in vivo. Swainsonine and other inhibitors of N-linked oligosaccharide processing may be useful anti-cancer drugs, a premise which has begun to be tested in humans.
Korczak
B
B
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Goss
P
P
Fernandez
B
B
Baker
M
M
Dennis
J W
JW
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D002240:Carbohydrate Sequence; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009844:Oligosaccharides / Q000032:analysis*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017026:Swainsonine / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D009363:Neoplasm Proteins; D009844:Oligosaccharides; D017026:Swainsonine