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DOI | 10.1126/science.aat5749 |
Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage | |
Park, Jung Wook1; Lee, John K.2; Sheu, Katherine M.3; Wang, Liang1; Balanis, Nikolas G.3; Kim Nguyen4; Smith, Bryan A.1; Cheng, Chen5; Tsai, Brandon L.1; Cheng, Donghui1; Huang, Jiaoti6; Kurdistani, Siavash K.5,7,8,9; Graeber, Thomas G.3,7,8,9,10; Witte, Owen N.1,3,7,8,9 | |
2018-10-05 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6410页码:91-95 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000446547100049 |
WOS关键词 | SMALL-CELL CARCINOMA ; PROSTATE-CANCER ; TRANSCRIPTION FACTORS ; RB LOSS ; EVOLUTION ; DIFFERENTIATION ; PLASTICITY ; RESISTANCE ; BCL-2 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/199725 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA; 2.Univ Calif Los Angeles, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA; 3.Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA; 4.Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA; 5.Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA; 6.Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA; 7.Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA; 8.Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA; 9.Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA; 10.Univ Calif Los Angeles, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA |
推荐引用方式 GB/T 7714 | Park, Jung Wook,Lee, John K.,Sheu, Katherine M.,et al. Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage[J]. SCIENCE,2018,362(6410):91-95. |
APA | Park, Jung Wook.,Lee, John K..,Sheu, Katherine M..,Wang, Liang.,Balanis, Nikolas G..,...&Witte, Owen N..(2018).Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.SCIENCE,362(6410),91-95. |
MLA | Park, Jung Wook,et al."Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage".SCIENCE 362.6410(2018):91-95. |
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