University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; UMass Metabolic Network; Davis Lab
Publication Date
2018-06-01
Document Type
Article
Disciplines
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Neoplasms
Abstract
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.
Keywords
JNK, breast cancer, cancer biology, cell biology, mouse, stress-activated MAPK
Rights and Permissions
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
10.7554/eLife.36389
Source
Elife. 2018 Jun 1;7. pii: 36389. doi: 10.7554/eLife.36389. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
eLife
PubMed ID
29856313
Repository Citation
Girnius, Nomeda A.; Edwards, Yvonne J. K.; Garlick, David S.; and Davis, Roger J., "The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation" (2018). University of Massachusetts Medical School Faculty Publications. 1584.
https://escholarship.umassmed.edu/faculty_pubs/1584
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Cellular and Molecular Physiology Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Neoplasms Commons