Journal
CANCER CELL
Volume 32, Issue 3, Pages 360-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.08.006
Keywords
-
Categories
Funding
- National Cancer Institute [R01CA043318, R01CA170550]
- NIH [R01CA121113, P30CA006973, U10CA180950]
- National Institute of Environments Health Sciences, National Institutes of Health [R01ES011858, R01ES023183]
- Hodson Trust
- Commonwealth Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- SU2C-DCS International Translational Cancer Research Dream Team [SU2C-AACR-DT1415]
Ask authors/readers for more resources
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adenosquamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available