MUC1号
癌症研究
糖基化
粘蛋白
癌变
生物
下调和上调
基因敲除
乳腺癌
基因沉默
癌症
免疫染色
免疫学
细胞培养
生物化学
免疫组织化学
遗传学
基因
作者
Jae‐Hyun Park,Toshihiko Nishidate,Kyoko Kijima,Takao Ohashi,Kaoru Takegawa,Tomoko Fujikane,Koichi Hirata,Yusuke Nakamura,Toyomasa Katagiri
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2010-03-10
卷期号:70 (7): 2759-2769
被引量:156
标识
DOI:10.1158/0008-5472.can-09-3911
摘要
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 beta-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.
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