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DOI | 10.1038/s41467-019-09988-z |
Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma | |
Natsuizaka, Mitsuteru1,2,3,4; Whelan, Kelly A.1,2,3; Kagawa, Shingo1,2,3,5; Tanaka, Koji1,2,3,6; Giroux, Veronique1,2,3; Chandramouleeswaran, Prasanna M.1,2,3; Long, Apple1,2,3; Sahu, Varun2,3,7; Darling, Douglas S.8,9; Que, Jianwen10; Yang, Yizeng1,2,3; Katz, Jonathan P.1,2,3; Wileyto, E. Paul2,3,11; Basu, Devraj2,3; Kita, Yoshiaki12; Natsugoe, Shoji12; Naganuma, Seiji13; Klein-Szanto, Andres J.14,15; Diehl, J. Alan16; Bass, Adam J.17; Wong, Kwok-Kin17,18; Rustgi, Anil K.3; Nakagawa, Hiroshi3 | |
2019-05-02 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan |
英文摘要 | Notch1 transactivates Notch3 to drive terminal differentiation in stratified squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be stochastically activated to promote carcinogenesis in murine models of SCC. Activated form of Notch1 promotes xenograft tumor growth when expressed ectopically. Here, we demonstrate that Notch1 activation and epithelial-mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in concert with transforming growth factor (TGF)-beta present in the tumor microenvironment. We find that TGF beta activates the transcription factor ZEB1 to repress Notch3, thereby limiting terminal differentiation. Concurrently, TGF beta drives Notch1-mediated EMT to generate tumor initiating cells characterized by high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC cells at the invasive tumor front and predicts for poor prognosis of esophageal SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000416292500004 |
WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; HUMAN ESOPHAGEAL KERATINOCYTES ; ZEB TRANSCRIPTION FACTORS ; GROWTH-FACTOR-BETA ; CANCER-CELLS ; TGF-BETA ; STEM-CELLS ; SIGNALING PATHWAY ; ORAL-CAVITY ; CROSS-TALK |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
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/204351 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Penn, Gastroenterol Div, Dept Med, Philadelphia, PA 19104 USA; 2.Abramson Canc Ctr, Philadelphia, PA 19104 USA; 3.Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA; 4.Hokkaido Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Sapporo, Hokkaido 0608638, Japan; 5.Chiba Univ, Grad Sch Med, Dept Gen Surg, Chiba, Chiba 2600856, Japan; 6.Osaka Univ, Dept Surg, Grad Sch Med, Gastroenterol Surg, Suita, Osaka 5650871, Japan; 7.Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA; 8.Univ Louisville, Dept Oral Immunol & Infect Dis, Louisville, KY 40202 USA; 9.Univ Louisville, Ctr Genet & Mol Med, Louisville, KY 40202 USA; 10.Columbia Univ, Div Digest & Liver Dis, Dept Med, New York, NY 10032 USA; 11.Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA; 12.Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Surg Breast & Thyroid Surg, Kagoshima 8908520, Japan; 13.Kochi Med Sch, Dept Pathol, Nankoku, Kochi 7838505, Japan; 14.Fox Chase Canc Ctr, Histopathol Facil, Philadelphia, PA 19111 USA; 15.Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA; 16.Med Univ South Carolina, Dept Biochem & Mol Biol, Hollings Canc Ctr, Charleston, SC 29425 USA; 17.Harvard Med Sch, Dept Med, Dana Farber Canc Inst, Boston, MA 02215 USA; 18.NYU, Div Hematol & Med Oncol, New York, NY 10016 USA |
推荐引用方式 GB/T 7714 | Natsuizaka, Mitsuteru,Whelan, Kelly A.,Kagawa, Shingo,et al. Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Natsuizaka, Mitsuteru.,Whelan, Kelly A..,Kagawa, Shingo.,Tanaka, Koji.,Giroux, Veronique.,...&Nakagawa, Hiroshi.(2019).Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.NATURE COMMUNICATIONS,8. |
MLA | Natsuizaka, Mitsuteru,et al."Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma".NATURE COMMUNICATIONS 8(2019). |
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