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学科主题: 基础医学
题名:
Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients
作者: Zhan, J.1,2,3; Niu, M.1,2,3; Wang, P.1,2,3; Zhu, X.1,4; Li, S.1,2,3; Song, J.1,2,3; He, H.1,4; Wang, Y.1,2,5; Xue, L.1,6; Fang, W.1,4; Zhang, H.1,2,3
关键词: HOXB9 ; colon adenocarcinoma ; differentiation ; mesenchymal-to-epithelial transition ; metastasis
刊名: BRITISH JOURNAL OF CANCER
发表日期: 2014-08-26
DOI: 10.1038/bjc.2014.387
卷: 111, 期:5, 页:883-893
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]: GENE-EXPRESSION ; TIGHT JUNCTIONS ; BREAST-CANCER ; COLORECTAL-CANCER ; HOMEOBOX B9 ; IN-VITRO ; METASTASIS ; TUMOR ; CARCINOMA ; GROWTH
英文摘要:

Background: Little is known about the tumour suppressive proteins and the underlying mechanisms that suppress colon cancer progression. Homeodomain-containing transcription factor HOXB9 plays an important role in embryogenesis and cancer development. We here aim to uncover the potential role of HOXB9 in the regulation of colon adenocarcinoma progression including epithelial-to-mesenchymal transition.

Methods: HOXB9 expression in colon adenocarcinoma cells and patients was analysed by western blot and immunohistochemistry separately. Correlation between HOXB9 expressions with patients′ survival was assessed by Kaplan-Meier analysis. HOXB9-regulated target gene expression was determined by RNA sequencing in HOXB9-overexpressing colon adenocarcinoma cells.

Results: Elevated HOXB9 expression was identified in well-differentiated colon adenocarcinoma patients and was associated with a better overall patients′ survival. Overexpression of HOXB9 inhibited colon adenocarcinoma cell growth, migration, invasion in vitro and tumour growth, liver as well as lung metastases in nude mice; whereas silencing HOXB9 promoted these functions. HOXB9 promoted colon adenocarcinoma differentiation via a mechanism that stimulates mesenchymal-to-epithelial transition, involving downregulation of EMT-promoting transcriptional factors including Snail, Twist, FOXC2 and ZEB1 and upregulation of epithelial proteins including E-cadherin, claudins-1, -4, -7, occludin and ZO-1.

Conclusions: HOXB9 is a novel tumour suppressor that inhibits colon adenocarcinoma progression by inducing differentiation. Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.

语种: 英语
所属项目编号: 2013CB910501 ; 2010CB912203 ; 2010CB529402 ; 81230051 ; 30830048 ; 31170711 ; 81321003 ; 81301802 ; 7120002 ; BMU20120314 ; BMU20130364
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:000341527100010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60655
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, Hlth Sci Ctr, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Lab Mol Cell Biol & Tumor Biol, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Lab Mol Pathol, Beijing 100191, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Res, Beijing 100191, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Dept Biochem, Beijing 100191, Peoples R China

Recommended Citation:
Zhan, J.,Niu, M.,Wang, P.,et al. Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients[J]. BRITISH JOURNAL OF CANCER,2014,111(5):883-893.
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