IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
Cholangiocarcinomas can originate from hepatocytes in mice
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
2012-08-01
DOI10.1172/JCI63212
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
WOS记录号WOS:000307128600027
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被引频次:158[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59255
专题北京大学临床肿瘤学院
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
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GB/T 7714
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.
APA Fan, Biao.,Malato, Yann.,Calvisi, Diego F..,Naqvi, Syed.,Razumilava, Nataliya.,...&Willenbring, Holger.(2012).Cholangiocarcinomas can originate from hepatocytes in mice.JOURNAL OF CLINICAL INVESTIGATION,122(8),2911-2915.
MLA Fan, Biao,et al."Cholangiocarcinomas can originate from hepatocytes in mice".JOURNAL OF CLINICAL INVESTIGATION 122.8(2012):2911-2915.
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