期刊
CELL RESEARCH
卷 26, 期 10, 页码 1149-1164出版社
SPRINGERNATURE
DOI: 10.1038/cr.2016.111
关键词
lung squamous cell carcinoma; molecular targeted therapy; exon array analyses; TRA2B-DNAH5 fusion; selumetinib
类别
资金
- Ministry of Science and Technology of China [2012CB910800]
- National Natural Science Foundation of China [81430066, 81402276, 81402371, 81401898, 81402498, 81101583, 81372509, 31370747, 81325015]
- Science and Technology Commission of Shanghai Municipality [12JC1409800, 15XD1504000]
- Cross and cooperation in science and technology innovation team program
- Chinese Postdoctoral foundation [2014M561536, 2013T60476]
- Shanghai Postdoctoral Foundation [14R21411400]
- Shanghai Institutes for Biological Sciences [2013KIP303, 2013KIP102, 2014KIP304]
Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion.
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