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

研究成果: ジャーナルへの寄稿学術誌査読

136 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)2759-2769
ページ数11
ジャーナルCancer Research
70
7
DOI
出版ステータス出版済み - 4月 1 2010

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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