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学科主题: 基础医学
题名:
Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family
作者: Yu, Yu1,2,3,4; Wu, Junzhou1,2,3,4; Guan, Lizhao1,2,3,4; Qi, Lihua1,2,3,4; Tang, Yan1,2,3,4; Ma, Bo1,2,3,4; Zhan, Jun1,2,3,4; Wang, Yunling1; Fang, Weigang1,5; Zhang, Hongquan1,2,3,4
关键词: breast cancer ; DNA methyltransferase ; Kindlins ; MicroRNA-200 family
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2013-09-15
DOI: 10.1002/ijc.28151
卷: 133, 期:6, 页:1368-1379
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: MITOGEN-INDUCIBLE GENE-2 ; MIR-200 FAMILY ; MESENCHYMAL TRANSITION ; DNA METHYLTRANSFERASE ; MIRNA PROMOTERS ; CELL INVASION ; ZEB1 ; METHYLATION ; EXPRESSION ; IDENTIFICATION
英文摘要:

Kindlin 2, as a focal adhesion protein, controls integrin activation and regulates Wnt signaling in an integrin-binding independent manner. However, the association of Kindlin 2 with cancer-related microRNAs is unknown. Here, we report that Kindlin 2 markedly downregulates the expression of miR-200 family by inducing CpG island hypermethylation. Mechanistically, Kindlin 2 forms a complex with DNMT3A in the cell nucleus and the two proteins co-occupy the promoter of miRNA-200b. Functionally, repression of miR-200b is required for Kindlin 2-induced breast cancer cell invasion and tumor formation. Our data indicate that Kindlin 2 plays a novel role in epigenetic repression of miR-200 family, a mechanism that promotes breast cancer invasion.

What′s new? Recent studies have implicated Kindlin 2, a focal adhesion protein, in boosting tumor progression. This study investigated the association of Kindlin 2 with microRNAs (miRNAs), which are frequently altered in cancer. The authors showed that Kindlin 2 forms a complex with DNA methyltransferase 3A, and this complex then blocks the miR-200b promoter. MicroRNAs in the miR-200 family function as tumor repressors, and their loss is crucial for cell invasion and tumor progression. These new results demonstrate for the first time that Kindlin 2 promotes breast cancer invasion by working together with DNA methyltransferase 3A to stifle miR-200b expression.

语种: 英语
所属项目编号: 2010CB912203 ; 2010CB529402 ; 30830048 ; 81230051 ; 31170711 ; 81101495 ; 7120002 ; BMU20120314
项目资助者: Ministry of Science and Technology of China ; National Natural Science Foundation of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Leading Academic Discipline Project of Beijing Education Bureau
WOS记录号: WOS:000321436300010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51285
Appears in Collections:基础医学院_解剖学与组织胚胎学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Minist Educ China, Key Lab Carcinogenesis & Translat Res, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Lab Mol Cell Biol & Tumor Biol, Dept Anat, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Histol, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Embryol, Beijing 100191, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China

Recommended Citation:
Yu, Yu,Wu, Junzhou,Guan, Lizhao,et al. Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family[J]. INTERNATIONAL JOURNAL OF CANCER,2013,133(6):1368-1379.
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