| Literature DB >> 27670699 |
Fei Li1,2,3,4, Zhaoyuan Fang5, Jian Zhang1,2,3,4, Chen Li1,2,3, Hongyan Liu1,2,3, Jufeng Xia1,2,3, Hongwen Zhu1,2,3,4, Chenchen Guo1,2,3,4, Zhen Qin1,2,3,4, Fuming Li1,2,3, Xiangkun Han1,2,3, Yuetong Wang1,2,3,4, Yan Feng1,2,3, Ye Wang1,2,3, Wenjing Zhang1,2,3,4, Zuoyun Wang1,2,3, Yujuan Jin1,2,3, Yihua Sun6,7, Wenyi Wei8, Rong Zeng1,2,9, Haiquan Chen6,7, Hongbin Ji1,2,3,9.
Abstract
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.Entities:
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Year: 2016 PMID： 27670699 PMCID： PMC5113306 DOI： 10.1038/cr.2016.111
Source DB: PubMed Journal: Cell Res ISSN： 1001-0602 Impact factor: 25.617