Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/45163
Title: EZH2-MEDIATED REPRESSION OF INTERFERON-Y RECEPTOR IN HUMAN CANCERS
Authors: WEE ZHEN NING
Keywords: EZH2, IFNGR1, prostate cancer, MYC, PI3K, H3K27me3
Issue Date: 3-Jul-2013
Source: WEE ZHEN NING (2013-07-03). EZH2-MEDIATED REPRESSION OF INTERFERON-Y RECEPTOR IN HUMAN CANCERS. ScholarBank@NUS Repository.
Abstract: The role of IFN-¿ signaling pathway in cancer is associated with immune surveillance and tumor suppression. In this study, we have identified IFNGR1 and components of the IFN-¿ signaling pathway to be down regulated in advanced cancers of prostate, breast, lung and liver. Importantly, we found that the expression of IFNGR1 was inversely correlated with the expression of EZH2 and MYC as the disease progresses to metastatic prostate cancer. Using MYC-driven prostate cancer as a model, we show that IFNGR1 is directly repressed by EZH2. EZH2 knockdown restored the expression of IFNGR1, when combined with interferon ¿ (IFN-¿) treatment, led to strong activation of IFN-STAT1 tumor suppressor pathway and robust apoptosis. Furthermore, we found that EZH2-mediated IFNGR1 silencing occurs widely in human malignances which this combination induced robust apoptosis. Thus, we identify an EZH2-inactivated IFN-signaling in human cancers, and patients carrying this deregulation may benefit from EZH2 and IFN-¿-targeted therapy.
URI: http://scholarbank.nus.edu.sg/handle/10635/45163
Appears in Collections:Ph.D Theses (Open)

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