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Cell Death Dis. 2018 Nov 16;9(12):1143. doi: 10.1038/s41419-018-1201-x.

NMT1 inhibition modulates breast cancer progression through stress-triggered JNK pathway.

Deng L1,2, Gao X2, Liu B1,2, He X1, Xu J1, Qiang J1, Wu Q2, Liu S3.

Author information

1
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Shanghai Medical College; Key Laboratory of Breast Cancer in Shanghai; Innovation Center for Cell Signaling Network; Cancer Institutes, Fudan University, 200032, Shanghai, China.
2
School of Life Science, The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, 230027, Hefei, Anhui, China.
3
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Shanghai Medical College; Key Laboratory of Breast Cancer in Shanghai; Innovation Center for Cell Signaling Network; Cancer Institutes, Fudan University, 200032, Shanghai, China. suling@fudan.edu.cn.

Abstract

Myristoylation is one of key post-translational modifications that involved in signal transduction, cellular transformation and tumorigenesis. Increasing evidence demonstrates that targeting myristoylation might provide a new strategy for eliminating cancers. However, the underlying mechanisms are still yielded unclear. In this study, we demonstrated that genetic inhibition of N-myristoyltransferase NMT1 suppressed initiation, proliferation and invasion of breast cancer cells either in vitro or in vivo. We identified ROS could negatively regulate NMT1 expression and NMT1 knockdown conversely promoted oxidative stress, which formed a feedback loop. Furthermore, inhibition of NMT1 caused degraded proteins increase and ER stress, which cross-talked with mitochondria to produce more ROS. And both of oxidative stress and ER stress could activate JNK pathway, leading to autophagy which abrogated breast cancer progression especially triple-negative breast cancer (TNBC). These studies provide a preclinical proof of concept for targeting NMT1 as a strategy to treat breast cancer.

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