期刊
CELL REPORTS
卷 9, 期 4, 页码 1318-1332出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.10.011
关键词
-
类别
资金
- NCI [P30CA125123]
- Breast Cancer Research Foundation (BCRF), NIH Grant [CA116167]
- NCI specialized program of research excellence (SPORE) in Breast Cancer [P50 CA166201]
- David and Margaret T. Grohne Family Foundation
- Ting Tsung and Wei Fong Chao Foundation
- DOD [BC094077]
- CPRIT [RP120583]
- Susan G. Komen for the Cure [KG090355]
- NIH [1R01CA178039-01, 5 T32 GM008231]
- DOD Breast Cancer Research Program [BC120604]
- CDMRP [542284, BC120604] Funding Source: Federal RePORTER
Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 (STP axis'') cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase beta TRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.
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