Journal
CANCER RESEARCH
Volume 73, Issue 24, Pages 7301-7312Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-1897
Keywords
-
Categories
Funding
- Canadian Institutes for Health Research [MOP 86731, 94867]
- Canadian Cancer Society [CCS20485]
- NCI Early Detection Research Network [U01CA0864021]
- Canary Foundation
- Vanier Canada Graduate Scholarship
- CIHR Jean-Francois Saint Denis Fellowship in Cancer Research
- CIHR Frederick Banting & Charles Best Canada Graduate Scholarship
- Banting Postdoctoral Fellowship
Ask authors/readers for more resources
Genetic analyses of lung cancer have helped found new treatments in this disease. Weconducted an integrative analysis of gene expression and copy number in 261 non-small cell lung cancers (NSCLC) relative to matched normal tissues to define novel candidate oncogenes, identifying 12q13-15 and more specifically the YEATS4 gene as amplified and overexpressed in similar to 20% of the NSCLC cases examined. Overexpression of YEATS4 abrogated senescence in human bronchial epithelial cells. Conversely, RNAi-mediated attenuation of YEATS4 in human lung cancer cells reduced their proliferation and tumor growth, impairing colony formation and inducing cellular senescence. These effects were associated with increased levels of p21WAF1 and p53 and cleavage of PARP, implicating YEATS4 as a negative regulator of the p21-p53 pathway. We also found that YEATS4 expression affected cellular responses to cisplastin, with increased levels associated with resistance and decreased levels with sensitivity. Taken together, our findings reveal YEATS4 as a candidate oncogene amplified in NSCLC, and a novel mechanism contributing to NSCLC pathogenesis. (C) 2013 AACR.
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