Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas

被引:44
|
作者
Kim, Il-Jin [1 ,2 ]
Quigley, David [2 ]
To, Minh D. [1 ,2 ]
Pham, Patrick [1 ]
Lin, Kevin [2 ]
Jo, Brian [2 ]
Jen, Kuang-Yu [2 ]
Raz, Dan [1 ]
Kim, Jae [1 ]
Mao, Jian-Hua [3 ]
Jablons, David [1 ,2 ]
Balmain, Allan [2 ,4 ]
机构
[1] Univ Calif San Francisco, Dept Surg, Thorac Oncol Lab, San Francisco, CA 94115 USA
[2] Univ Calif San Francisco, Helen Diller Family Canc Ctr, San Francisco, CA 94143 USA
[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
[4] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
来源
NATURE COMMUNICATIONS | 2013年 / 4卷
关键词
THYROID TRANSCRIPTION FACTOR-1; SEGREGATING MOUSE-POPULATION; GENETIC ARCHITECTURE; TUMOR SUSCEPTIBILITY; ACQUIRED-RESISTANCE; AUTOREGULATORY LOOP; BREAST-CANCER; KINASE; EXPRESSION; PROTEIN;
D O I
10.1038/ncomms2660
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Analysis of gene expression patterns in normal tissues and their perturbations in tumours can help to identify the functional roles of oncogenes or tumour suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumours includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumour-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of poly (ADP-ribose) polymerase signalling to inhibit growth of lung tumour cells. Targeting of genes that are recruited into tumour mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes.
引用
收藏
页数:11
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