中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 计算技术研究所
  3. 中国科学院计算技术研究所
  4. 中国科学院计算技术研究所期刊论文
  5. 英文
热门
Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade

文献类型：期刊论文

作者Ma, Jianhui2,3,4; Meng, Yan2,3,5; Kwiatkowski, David J.6; Chen, Xinxin2,3; Feng, Haiyong2,3; Sun, Qian2,3; Zha, Xiaojun2,3; Wang, Fang2,3; Wang, Ying2,3; Jing, Yanling2,3
刊名JOURNAL OF CLINICAL INVESTIGATION
出版日期2010
卷号120期号:1页码:103-114
ISSN号0021-9738
DOI10.1172/JCI37964
英文摘要The receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) pathway is frequently altered in cancer, but the underlying mechanism leading to tumorigenesis by activated mTOR remains less clear. Here we show that mTOR is a positive regulator of Notch signaling in mouse and human cells, acting through induction of the STAT3/p63/jagged signaling cascade. Furthermore, in response to differential cues from mTOR, we found that Notch served as a molecular switch to shift the balance between cell proliferation and differentiation. We determined that hyperactive mTOR signaling impaired cell differentiation of murine embryonic fibroblasts via potentiation of Notch signaling. Elevated mTOR signaling strongly correlated with enhanced Notch signaling in poorly differentiated but not in well-differentiated human breast cancers. Both human lung lymphangioleiomyomatosis (LAM) and mouse kidney tumors with hyperactive mTOR due to tumor suppressor TSC1 or TSC2 deficiency exhibited enhanced STAT3/p63/Notch signaling. Furthermore, tumorigenic potential of cells with uncontrolled mTOR signaling was suppressed by Notch inhibition. Our data therefore suggest that perturbation of cell differentiation by augmented Notch signaling might be responsible for the underdifferentiated phenotype displayed by certain tumors with an aberrantly activated RTK/PI3K/AKT/mTOR pathway. Additionally, the STAT3/p63/Notch axis may be a useful target for the treatment of cancers exhibiting hyperactive mTOR signaling.
资助项目National Natural Science Foundation of China[30772466] ; National Natural Science Foundation of China[30788004] ; National Natural Science Foundation of China[30872840] ; National Natural Science Foundation of China[30971503] ; National Basic Research Program of China (973 Program)[2009CB522203] ; National Basic Research Program of China (973 Program)[2009CBS22106] ; Innovation Project of Key Laboratory of Ophthalmology ; NIH National Cancer Institute[1P01CA120964]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000273495700017
出版者AMER SOC CLINICAL INVESTIGATION INC
源URL[http://119.78.100.204/handle/2XEOYT63/12080]  
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Zhang, Hongbing
作者单位1.Peking Union Med Coll, Inst Basic Med Sci, Dept Physiol, Beijing 100005, Peoples R China
2.Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Dept Physiol & Pathophysiol, Beijing 100730, Peoples R China
3.Chinese Acad Med Sci, Sch Basic Med, Beijing 100037, Peoples R China
4.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Lab Ocular Genet, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China
5.Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Excellence Tissue Engn, Beijing 100730, Peoples R China
6.Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Translat Med,Dept Med, Boston, MA 02115 USA
7.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Surg, Div Breast Surg, Beijing 100037, Peoples R China
8.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Med, Div Resp Med, Beijing 100037, Peoples R China
9.N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA
10.Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
推荐引用方式
GB/T 7714		 Ma, Jianhui,Meng, Yan,Kwiatkowski, David J.,et al. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade[J]. JOURNAL OF CLINICAL INVESTIGATION,2010,120(1):103-114.
APA Ma, Jianhui.,Meng, Yan.,Kwiatkowski, David J..,Chen, Xinxin.,Feng, Haiyong.,...&Zhang, Hongbing.(2010).Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade.JOURNAL OF CLINICAL INVESTIGATION,120(1),103-114.
MLA Ma, Jianhui,et al."Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade".JOURNAL OF CLINICAL INVESTIGATION 120.1(2010):103-114.

入库方式： OAI收割

来源：计算技术研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。