Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis

Jae Hyun Park, Toshihiko Nishidate, Kyoko Kijima, Takao Ohashi, Kaoru Takegawa, Tomoko Fujikane, Koichi Hirata, Yusuke Nakamura, Toyomasa Katagiri

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The structure of O-glycosylated proteins is altered in breast cancer cells, but the mechanisms of such an aberrant modification have been largely unknown. We here report critical roles of a novel druggable target, polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which is upregulated in a great majority of breast cancers and encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation. Knockdown of GALNT6 by small interfering RNA significantly enhanced cell adhesion function and suppressed the growth of breast cancer cells. Western blot and immunostaining analyses indicated that wild-type GALNT6 protein could glycosylate and stabilize an oncoprotein mucin 1 (MUC1), which was upregulated with GALNT6 in breast cancer specimens. Furthermore, knockdown of GALNT6 or MUC1 led to similar morphologic changes of cancer cells accompanied by the increase of cell adhesion molecules β-catenin and E-cadherin. Our findings implied that overexpression of GALNT6 might contribute to mammary carcinogenesis through aberrant glycosylation and stabilization of MUC1 and that screening of GALNT6 inhibitors would be valuable for the development of novel therapeutic modalities against breast cancer.

Original languageEnglish
Pages (from-to)2759-2769
Number of pages11
JournalCancer Research
Volume70
Issue number7
DOIs
Publication statusPublished - Apr 1 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis'. Together they form a unique fingerprint.

  • Cite this

    Park, J. H., Nishidate, T., Kijima, K., Ohashi, T., Takegawa, K., Fujikane, T., Hirata, K., Nakamura, Y., & Katagiri, T. (2010). Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis. Cancer Research, 70(7), 2759-2769. https://doi.org/10.1158/0008-5472.CAN-09-3911