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学科主题: 基础医学
题名:
Kindlin-2 induced by TGF-beta signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9
作者: Zhan, Jun1,2,3; Song, Jiagui1,2,3; Wang, Peng1,2,3; Chi, Xiaochun1,2,3; Wang, Yunling1,2,3; Guo, Yongqing4; Fang, Weigang1,2,5; Zhang, Hongquan1,2,3
关键词: Kindlin-2 ; TGF-beta 1 ; HOXB9 ; Pancreatic cancer ; E-cadherin
刊名: CANCER LETTERS
发表日期: 2015-05-28
DOI: 10.1016/j.canlet.2015.02.039
卷: 361, 期:1, 页:75-85
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]: GASTRIC-CANCER CELLS ; BREAST-CANCER ; MESENCHYMAL TRANSDIFFERENTIATION ; INTEGRIN ACTIVATION ; HOMEOBOX GENE ; IN-VITRO ; EXPRESSION ; METASTASIS ; ADHESION ; TUMOR
英文摘要:

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with no effective therapeutics. Invasion and metastasis are the major characteristics of PDAC. However, mechanisms underlying PDAC invasion and metastasis are elusive. In this report, we found that Kindlin-2 is a target protein of transforming growth factor beta (TGF-beta) signaling and is upregulated by TGF-beta 1 in PDAC cells. TGF-beta 1-upregulated Kindlin-2 promotes PDAC cell growth, migration and invasion, whereas Kindlin-2 upregulates transforming growth factor receptor I (T beta RI), a key component of TGF-beta signaling. Thereby Kindlin-2 and TGF-beta signaling constitute a positive feedback loop. Mechanistically, Kindlin-2 promotes PDAC progression by downregulation of HOXB9 and E-cadherin. For clinical relevance, enhanced expression of Kindlin-2 predicts a poor overall survival for PDAC patients. Gene expression levels of Kindlin-2, TGF-beta, VIZI and HOXB9 are all correlated with the overall survival of PDAC patients in an Oncomine dataset. Taken together, our findings demonstrated that TGF-beta 1-induced Kindlin-2 expression promotes PDAC progression by downregulation of HOXB9 and E-cadherin. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

语种: 英语
所属项目编号: 2015CB553906 ; 2013CB910501 ; 2013ZX09401004-006 ; 81230051 ; 81472734 ; 31170711 ; 81321003 ; 30830048 ; 81301802 ; 7120002 ; BMU20120314 ; BMU20130364 ; BMU20130373 ; BMU20110254
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:000352675500010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66362
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Minist Educ, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Dept Anat Histol & Embryol, Lab Mol Cell Biol & Tumor Biol, Beijing 100191, Peoples R China
4.Sinojapan Friendship Hosp, Dept Thorac Surg, Beijing 100123, Peoples R China
5.Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Zhan, Jun,Song, Jiagui,Wang, Peng,et al. Kindlin-2 induced by TGF-beta signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9[J]. CANCER LETTERS,2015,361(1):75-85.
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