Volume 26 Issue 10, October 2016: 1149-1164
ORIGINAL ARTICLES
Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma
Fei Li1,2,3,4,*, Zhaoyuan Fang8,*, 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 Wei9, Rong Zeng1,2,5, Haiquan Chen6,7 and Hongbin Ji1,2,3,5
1Key Laboratory of Systems Biology, Shanghai 200031, China
2CAS Center for Excellence in Molecular Cell Science, Shanghai 200031, China
3Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China
4University of Chinese Academy of Sciences, Beijing 100049, China
5School of Life Science and Technology, Shanghai Tech University, Shanghai 200120, China
6Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
7Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
8Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
9Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Correspondence: Hongbin Ji,(hbji@sibcb.ac.cn)
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.
10.1038/cr.2016.111
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