Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/34731
Title: SUMOYLATION OF NEMO AND NF-KB ACTIVATION BY AN RNA HELICASE, DP103 DEFINES THE METASTATIC POTENTIAL OF HUMAN BREAST CANCERS
Authors: HAY HUI SIN
Keywords: Breast cancer, metastasis, DP103, SUMOylation, NF-kB, genotoxic stress
Issue Date: 10-Jan-2012
Source: HAY HUI SIN (2012-01-10). SUMOYLATION OF NEMO AND NF-KB ACTIVATION BY AN RNA HELICASE, DP103 DEFINES THE METASTATIC POTENTIAL OF HUMAN BREAST CANCERS. ScholarBank@NUS Repository.
Abstract: Mortality from breast cancer is almost entirely the result of invasion and metastasis of neoplastic cells; therefore, understanding gene products involved in breast cancer metastasis is an important research goal. We discovered DP103, a RNA helicase, to be correlated with the level of maglinancies and its suppression led to the decreased ability of breast cancer cells to migrate and invade. We screened a panel of breast cancer cell lines and show highly metastatic cell lines like MDA-MB-231 and BT549 display high expression levels of MMP9 and are highly correlated to DP103 levels. We next show via EMSA and luciferase reporter assay that decrease in MMP9 levels is regulated by NF-¿B and not AP-1. Additionally, under the stimulation of known NF-¿B genotoxic agents, NF-¿B activity was decreased when DP103 was knockdown. We also discovered that DP103 coimmunoprecipitated with NEMO and is required for the SUMOylation of NEMO upon genotoxic stress. Downregulation of DP103 abrogated this modification to occur. Additionally, we observed that DP103 enhances the interaction of NEMO and PIASy while decreasing that of NEMO and SENP2. Together, our study identifies DP103 as the ¿missing¿ key regulator of NF-kB activation under genotoxic stress. Importantly, DP103 is a novel prognostic marker that identifies patients who are at risk for developing metastases, thus enabling oncologists to begin tailoring treatment strategies to individual patients.
URI: http://scholarbank.nus.edu.sg/handle/10635/34731
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