期刊
CELL
卷 166, 期 4, 页码 963-976出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.06.056
关键词
-
资金
- Cancer Center Support grant [5P30CA045508, P30CA008748]
- CSHL Association
- NIH [5P30CA45508-26, 5P50CA101955-07, 1U10CA180944-01, 5U01CA168409-3, 1R01CA190092-01, AG040020, CA152559, R01 CA159222]
- Carcinoid Foundation
- PCUK
- David Rubinstein Center for Pancreatic Cancer Research at MSKCC
- Stand Up to Cancer/KWF
- STARR Foundation [I7-A718]
- DOD [W81XWH-13-PRCRP-IA]
- Precision Medicine Research Associates
- Damon Runyon Cancer Research Foundation [DRG-2165-13]
- Human Frontier Science Program [LT000190/2013]
- Cancer Research Society
- CCSRI [702317]
- Canadian Institute of Health Research
- Swedish Research Council [537-2013-7277]
- Sociedad Espanola de Oncologia Medica (SEOM)
- Hope Funds for Cancer Research Fellowship
Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
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