Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis.
Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and beta 1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAc beta 1-6Man alpha 1-6Man beta 1-). However, little is known about the relevant glycoproteins or how these transformation-related changes in oligosaccharide biosynthesis may affect the malignant phenotype. Here it is reported that a cell surface glycoprotein, gp 130, is a major target of increased beta 1-6-linked branching and that the expression of these oligosaccharide structures is directly related to the metastatic potential of the cells. Glycosylation mutants of a metastatic tumor cell line were selected that are deficient in both beta 1-6 GlcNAc transferase V activity and metastatic potential in situ. Moreover, induction of increased beta 1-6 branching in clones of a nonmetastatic murine mammary carcinoma correlated strongly with acquisition of metastatic potential. The results indicate that increased beta 1-6-linked branching of complex-type oligosaccharides on gp 130 may be an important feature of tumor progression related to increased metastatic potential.
D000818:Animals; D001216:Asparagine; D002236:Carbohydrate Conformation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005964:Glucosyltransferases / Q000378:metabolism; D006031:Glycosylation; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D009844:Oligosaccharides / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D052118:Lysosomal-Associated Membrane Protein 1
D001216:Asparagine; D005964:Glucosyltransferases; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017351:N-Acetylglucosaminyltransferases; D009844:Oligosaccharides; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase