O-GlcNAcylation of Cofilin Promotes Breast Cancer Cell Invasion

doi:10.1074/jbc.M113.495713

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	O-GlcNAcylation of Cofilin Promotes Breast Cancer Cell Invasion
	Huang, Xun2 ; Pan, Qiuming 2; Sun, Danni 2; Chen, Wei 1; Shen, Aijun2 ; Huang, Min2 ; Ding, Jian2 ; Geng, Meiyu2
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2013-12-20
卷号	288 期号:51 页码:36418-36425
关键词	Breast Cancer Cell Invasion Cell Motility Cofilin O-GlcNAcylation Invadopodia OGT
ISSN号	0021-9258
DOI	10.1074/jbc.M113.495713
文献子类	Article
英文摘要	Background:O-GlcNAcylation plays important roles in breast cancer metastasis, but the underlying mechanism is not fully known. Results: Cofilin is O-GlcNAcylated at Ser-108, which is required for its proper localization in invadopodia and is implicated in promoting breast cancer cell invasion. Conclusion:O-GlcNAcylation plays an important role in fine-tuning the regulation of cofilin. Significance: These findings reveal the implications of aberrant cofilin O-GlcNAcylation in cancer metastasis. O-GlcNAcylation is a post-translational modification that regulates a broad range of nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes. Previous studies have shown that increased levels of global O-GlcNAcylation and O-GlcNAc transferase (OGT) are linked to the incidence of metastasis in breast cancer patients, but the molecular basis behind this is not fully known. In this study, we have determined that the actin-binding protein cofilin is O-GlcNAcylated by OGT and mainly, if not completely, mediates OGT modulation of cell mobility. O-GlcNAcylation at Ser-108 of cofilin is required for its proper localization in invadopodia at the leading edge of breast cancer cells during three-dimensional cell invasion. Loss of O-GlcNAcylation of cofilin leads to destabilization of invadopodia and impairs cell invasion, although the actin-severing activity or lamellipodial localization is not affected. Our study provides insights into the mechanism of post-translational modification in fine-tuning the regulation of cofilin activity and suggests its important implications in cancer metastasis.
资助项目	Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81302791]
WOS关键词	N-ACETYLGLUCOSAMINE ; LIM-KINASE ; METASTASIS ; GLCNAC ; PHOSPHORYLATION ; ADF/COFILIN ; MIGRATION ; PATHWAY ; DYNAMICS ; MOTILITY
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000328883400023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277331]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian
作者单位	1.China Pharmaceut Univ, Ctr Drug Discovery, State Key Lab Nat Med, Nanjing 210009, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Huang, Xun,Pan, Qiuming,Sun, Danni,et al. O-GlcNAcylation of Cofilin Promotes Breast Cancer Cell Invasion[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(51):36418-36425.
APA	Huang, Xun.,Pan, Qiuming.,Sun, Danni.,Chen, Wei.,Shen, Aijun.,...&Geng, Meiyu.(2013).O-GlcNAcylation of Cofilin Promotes Breast Cancer Cell Invasion.JOURNAL OF BIOLOGICAL CHEMISTRY,288(51),36418-36425.
MLA	Huang, Xun,et al."O-GlcNAcylation of Cofilin Promotes Breast Cancer Cell Invasion".JOURNAL OF BIOLOGICAL CHEMISTRY 288.51(2013):36418-36425.