The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation
UMass Chan AffiliationsDavis Lab
UMass Metabolic Network
Program in Molecular Medicine
Document TypeJournal Article
Biochemistry, Biophysics, and Structural Biology
Cell and Developmental Biology
Cellular and Molecular Physiology
Enzymes and Coenzymes
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AbstractBreast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent loss-of-function mutations in components of the cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor suppressive function was not mediated by a role of JNK in the growth of established tumors, but by a requirement of JNK to prevent tumor initiation. Together, these data identify JNK pathway defects as 'driver' mutations that promote genome instability and tumor initiation.
Elife. 2018 Jun 1;7. pii: 36389. doi: 10.7554/eLife.36389. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29357
RightsCopyright: © 2018, Girnius et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2018, Girnius et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.