BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization.
BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization.
复制标题
DOI：
10.1158/0008-5472.can-14-0061
复制
发表时间：
2014-11-15
期刊：
影响因子：
11.2
通讯作者：
Weissman B
中科院分区：
文献类型：
--
作者：
Orvis T;Hepperla A;Walter V;Song S;Simon J;Parker J;Wilkerson MD;Desai N;Major MB;Hayes DN;Davis IJ;Weissman B
SWI/SNF chromatin remodeling complexes regulate critical cellular processes including cell cycle control, programmed cell death, differentiation, genomic instability and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver and pediatric cancers. In particular, ~10% of primary human lung non-small lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes.
