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

Link to Article in PubMed

Journal/Book/Conference Title

eLife

PubMed ID

29856313

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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