title: Polypeptide N-acetylgalactosaminyltransferase 6 disrupts mammary acinar morphogenesis through O-glycosylation of fibronectin.
abstract: A high expression of short and immature O-glycans is one of the prominent features of breast cancer cells, which would be attributed to the upregulated expression of glycosyltransferases. Therefore, a detailed elucidation of glycosyltransferases and their substrate(s) may improve our understandings for their roles in mammary carcinogenesis. Here we report that overexpression of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), a glycosyltransferase involved in the initial step of O-glycosylation, has transformational potentials through disruptive acinar morphogenesis and cellular changes similar to epithelial-to-mesenchymal transition in normal mammary epithelial cell, MCF10A. As one of the critical O-glycan substrates, we identified fibronectin that was O-glycosylated in vivo and thereby stabilized by GALNT6. Because knockdown of fibronectin abrogated the disruptive proliferation caused by introduction of GALNT6 into epithelial cells, our findings suggest that GALNT6-fibronectin pathway should be a critical component for breast cancer development and progression.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.forename: Suyoun
authors.initials: S
authors.lastname: Chung
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kijima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D018450:Disease Progression; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D042361:Mammary Glands, Human / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics*; D017350:N-Acetylgalactosaminyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055550:Protein Stability; D014162:Transfection; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D005353:Fibronectins; D007527:Isoenzymes; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase