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学科主题基础医学
Opposite Role of Kindlin-1 and Kindlin-2 in Lung Cancers
Zhan, Jun2,3; Zhu, Xiang2,4; Guo, Yongqing1; Wang, Yunling2,5; Wang, Yuxiang2,4; Qiang, Guangliang1; Niu, Miaomiao2,3; Hu, Jinxia2,3; Du, Juan2,3; Li, Zhilun6; Cui, Jia2,3; Ma, Bo2,3; Fang, Weigang2,4; Zhang, Hongquan2,3
刊名PLOS ONE
2012-11-29
DOI10.1371/journal.pone.0050313
7期:11
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者Ministry of Science and Technology of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Center for Biosciences at Karolinska Institutet ; National Natural Science Foundation of China (NSFC) ; Ministry of Science and Technology of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Center for Biosciences at Karolinska Institutet ; National Natural Science Foundation of China (NSFC)
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]KINDLER-SYNDROME ; ADHESION ; PROTEIN ; FAMILY ; METASTASIS ; MUTATIONS ; GROWTH ; DOMAIN
英文摘要

Lung cancer is highly heterogenous and is composed of various subtypes that are in diverse differential stages. The newly identified integrin-interacting proteins Kindlin-1 and Kindlin-2 are the activators of transmembrane receptor integrins that play important roles in cancer progression. In this report we present the expression profiles of Kindlin-1 and Kindlin-2 in lung cancers using patient specimens and established their correlation with lung cancer progression. We found that Kindlin-1 was expressed in epithelia-derived non-small-cell lung cancer, especially in squamous cell lung cancer but expressed at low levels in poorly differentiated large cell lung cancer. However, Kindlin-2 was highly expressed in large cell lung cancer. Both Kindlin-1 and Kindlin-2 were found not expressed or expressed at very low levels in neuroendocrine-derived small cell lung cancer. Importantly, the Kindlin-1 expression level was positively correlated with the differentiation of squamous cell lung cancer. Surprisingly, we found that the very homologous Kindlin family proteins, Kindlin-1 and Kindlin-2, displayed counteracting functional roles in lung cancer cells. Ectopic expression of Kindlin-1 in non-small-cell lung cancer cells inhibited in vitro cell migration and in vivo tumor growth, while Kindlin-2 promoted these functions. Mechanistically, Kindlin-1 prohibited epithelail to mesenchymal transition in non-small-cell lung cancer cells, while Kindlin-2 enhanced epithelail to mesenchymal transition in these cells. Taken together, we demonstrated that Kindlin-1 and Kindlin-2 differentially regulate lung cancer cell progression. Further, the expression levels of Kindlin-1 might be potentially used as a marker for lung cancer differentiation and targeting Kindlin-2 might block the invasive growth of large cell lung cancer.

语种英语
所属项目编号2010CB912203 ; 2010CB529402 ; NSFC31170711 ; 7120002 ; 30830048
资助者Ministry of Science and Technology of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Center for Biosciences at Karolinska Institutet ; National Natural Science Foundation of China (NSFC) ; Ministry of Science and Technology of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Center for Biosciences at Karolinska Institutet ; National Natural Science Foundation of China (NSFC)
WOS记录号WOS:000312104900038
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51100
专题基础医学院_病理学系
作者单位1.Sino Japan Friendship Hosp, Dept Thorac Surg, Beijing, Peoples R China
2.Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Lab Mol Cell Biol & Tumor Biol, Dept Anat Histol & Embryol, Beijing 100871, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Res, Beijing 100871, Peoples R China
6.Karolinska Inst, Unit Clin Mol Biol, Dept Biosci & Nutr, Huddinge, Sweden
推荐引用方式
GB/T 7714
Zhan, Jun,Zhu, Xiang,Guo, Yongqing,et al. Opposite Role of Kindlin-1 and Kindlin-2 in Lung Cancers[J]. PLOS ONE,2012,7(11).
APA Zhan, Jun.,Zhu, Xiang.,Guo, Yongqing.,Wang, Yunling.,Wang, Yuxiang.,...&Zhang, Hongquan.(2012).Opposite Role of Kindlin-1 and Kindlin-2 in Lung Cancers.PLOS ONE,7(11).
MLA Zhan, Jun,et al."Opposite Role of Kindlin-1 and Kindlin-2 in Lung Cancers".PLOS ONE 7.11(2012).
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