The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation

• DOI: 10.7554/elife.36389
• Publication Date: 2018-06-01T11:01:09Z
• Authors: Nomeda Girnius; Yvonne JK Edwards; David S Garlick; Roger J Davis
• Keywords: 0301 basic medicine; 570; QH301-705.5; Carcinogenesis; Cell Survival; MAP Kinase Signaling System; Science; Biophysics; 610; Breast Neoplasms; Biochemistry; Genomic Instability; Cell and Developmental Biology; 03 medical and health sciences; breast cancer; Neoplasms; cell biology; Enzymes and Coenzymes; Animals; Humans; Exome; Biology (General); mouse; cancer biology; Cancer Biology; Cell Proliferation; Q; R; JNK Mitogen-Activated Protein Kinases; Epithelial Cells; 3. Good health; Cellular and Molecular Physiology; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Disease Models, Animal; Phenotype; stress-activated MAPK; and Structural Biology; Neoplastic Stem Cells; Medicine; Female; JNK; Genetic Phenomena

Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast genomic DNA indicates frequent loss-of-function mutations components cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK can promote cell proliferation by activating AP1 transcription factor, this apparent association reduced with tumor development was unexpected. We examined effect deficiency murine epithelium. Loss caused instability and cancer. Moreover, widespread early neoplasia rapid formation a model This suppressive function not mediated role growth established tumors, but requirement to prevent initiation. Together, these data identify pathway defects as 'driver' that genome