Program in Molecular Medicine; UMass Metabolic Network; Davis Lab
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Neoplasms
Breast 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.
JNK, breast cancer, cancer biology, cell biology, mouse, stress-activated MAPK
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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.
DOI of Published Version
Elife. 2018 Jun 1;7. pii: 36389. doi: 10.7554/eLife.36389. Link to article on publisher's site
Girnius NA, Edwards YJ, Garlick DS, Davis RJ. (2018). The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.7554/eLife.36389. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1584
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