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学科主题: 临床医学
题名:
Cholangiocarcinomas can originate from hepatocytes in mice
作者: Fan, Biao1,2,3; Malato, Yann4,5; Calvisi, Diego F.6; Naqvi, Syed4; Razumilava, Nataliya7; Ribback, Silvia6; Gores, Gregory J.7; Dombrowski, Frank6; Evert, Matthias6; Chen, Xin1,8; Willenbring, Holger4,5,8
刊名: JOURNAL OF CLINICAL INVESTIGATION
发表日期: 2012-08-01
DOI: 10.1172/JCI63212
卷: 122, 期:8, 页:2911-2915
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: INTRAHEPATIC CHOLANGIOCARCINOMA ; CLINICOPATHOLOGICAL SIGNIFICANCE ; LIVER ; EXPRESSION ; DIFFERENTIATION ; INSIGHTS
英文摘要:

Intrahepatic cholangiocarcinomas (ICCs) are primary liver tumors with a poor prognosis. The development of effective therapies has been hampered by a limited understanding of the biology of ICCs. Although ICCs exhibit heterogeneity in location, histology, and marker expression, they are currently thought to derive invariably from the cells lining the bile ducts, biliary epithelial cells (BECs), or liver progenitor cells (LPCs). Despite lack of experimental evidence establishing BECs or LPCs as the origin of ICCs, other liver cell types have not been considered. Here we show that ICCs can originate from fully differentiated hepatocytes. Using a mouse model of hepatocyte fate tracing, we found that activated NOTCH and AKT signaling cooperate to convert normal hepatocytes into biliary cells that act as precursors of rapidly progressing, lethal ICCs. Our findings suggest a previously overlooked mechanism of human ICC formation that may be targetable for anti-ICC therapy.

语种: 英语
所属项目编号: RN2-00950 ; R01 CA136606 ; Ev168/2-1 ; Do622/2-1 ; P30 DK026743 ; 2010601079
项目资助者: California Institute for Regenerative Medicine (CIRM) New Faculty ; NIH ; Deutsche Forschungsgemeinschaft (DFG) ; UCSF Liver Center ; China Scholarship Council
WOS记录号: WOS:000307128600027
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59255
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
2.UCSF, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA
3.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Surg, Beijing 100871, Peoples R China
4.Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China
5.UCSF, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
6.UCSF, Div Transplantat, Dept Surg, San Francisco, CA 94143 USA
7.Ernst Moritz Arndt Univ Greifswald, Inst Pathol, Greifswald, Germany
8.UCSF, Ctr Liver, San Francisco, CA 94143 USA

Recommended Citation:
Fan, Biao,Malato, Yann,Calvisi, Diego F.,et al. Cholangiocarcinomas can originate from hepatocytes in mice[J]. JOURNAL OF CLINICAL INVESTIGATION,2012,122(8):2911-2915.
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