期刊
CANCER CELL
卷 23, 期 3, 页码 362-375出版社
CELL PRESS
DOI: 10.1016/j.ccr.2013.01.025
关键词
-
资金
- National Institutes of Health [RO1CA133379, RO1CA105129, 1RO1CA173636, RO1CA149655, RO1GM088847]
- Leukemia and Lymphoma Society
- Chemotherapy Foundation
- William Lawrence Blanche Hughes Foundation
- V Foundation for Cancer Research
- NIH
- NYU Hematology/Oncology NIH [5T32HL007151-33]
- NIH [1T32CA160002-01]
- Alexander von Humboldt Foundation
- Grants-in-Aid for Scientific Research [22130001, 24501305] Funding Source: KAKEN
The molecular mechanisms regulating leukemia-initiating cell (LIC) function are of important clinical significance. We use chronic myelogenous leukemia (CML) as a model of LIC-dependent malignancy and identify the interaction between the ubiquitin ligase Fbw7 and its substrate c-Myc as a regulator of LIC homeostasis. Deletion of Fbw7 leads to c-Myc overexpression, p53-dependent LIC-specific apoptosis, and the eventual inhibition of tumor progression. A decrease of either c-Myc protein levels or attenuation of the p53 response rescues LIC activity and disease progression. Further experiments showed that Fbw7 expression is required for survival and maintenance of human CML LIC. These studies identify a ubiquitin ligase:substrate pair regulating LIC activity, suggesting that targeting of the Fbw7:c-Myc axis is an attractive therapy target in refractory CML.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据