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J Biol Chem. 2015 Aug 14;290(33):20159-66. doi: 10.1074/jbc.M115.654483. Epub 2015 Jun 29.

Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice.

Author information

1
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104.
2
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
3
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, 215006 Suzhou, China.
4
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, China-Japan Union Hospital of Jilin University, 130033 Changchun, China, and.
5
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009 Nanjing, China.
6
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, hong-chen@omrf.org.
7
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, 215006 Suzhou, China, lijun-xia@omrf.org.

Abstract

Mucin-type core 1-derived O-glycans, one of the major types of O-glycans, are highly expressed in mammary gland epithelium. Abnormal O-glycans such as Tn antigen are found in over 90% of breast cancers; however, the in vivo role of these aberrant O-glycans in the etiology of breast cancer is unclear. We generated mice with mammary epithelial specific deletion of core 1-derived O-glycans. By crossing with two spontaneous mouse breast cancer models, we determined that loss of core 1-derived O-glycans delays the onset and progression of breast cancer development. Deficiency of core 1 O-glycosylation impaired the localization of Muc1, a major O-glycoprotein, on the apical surfaces of mammary epithelium. Signaling mediated by Muc1, which is critical for breast cancer development, was also defective in the absence of core 1 O-glycans. This study reveals an unexpected role of core 1-derived O-glycans in breast cancer development in mice.

KEYWORDS:

breast cancer; cell proliferation; glycosylation; mouse; mucin 1, cell surface associated (MUC1); tumor microenvironment

PMID:
26124270
PMCID:
PMC4536426
DOI:
10.1074/jbc.M115.654483
[Indexed for MEDLINE]
Free PMC Article

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