Lung cancer is the leading cause of cancer-related death worldwide. Non-Small Cell Lung Cancer (NSCLC) accounts for about 80% of all lung cancer cases, which is composed of two major subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Identification of oncogenic drivers has significantly reformed the current strategies for lung cancer treatment in clinic and initiated the era of personalized therapy. Despite of advanced knowledge of oncogenic drivers in human lung ADC, it remains largely unknown about the potential oncogenic drivers in human lung SCC. Recently, a team of researchers led by Dr. JI Hongbin, at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, CAS, have identified TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung SCC.
Research in the JI lab mainly focus on lung cancer genomics studies and aim to identify essential oncogenic drivers via systematic genomic analyses. Through exon array analyses, molecular analyses and functional studies, LI Fei, FANG Zhaoyuan and ZHANG Jian together with other lab members in the lab have successfully identified the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC.
This gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Then through mechanistic studies, researchers further found that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. Researchers showed that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression.
These findings improved our current knowledge of oncogenic drivers in lung SCC and provided a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion.
This work, entitled “Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma” was published in the journal Cell Research on Sep 27th, 2016.
This work was supported by the grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Chinese Postdoctoral foundation, the Shanghai Postdoctoral Foundation and the Shanghai Institutes for Biological Sciences.
Legend: (A) Exon array analyses of 65 lung SCC specimens and 5 paired normal lung tissues identified a potential DNAH5 fusion in lung SCC sample 207LC. The potential fusion site was indicated by the arrow. (B) The schematic diagram of TRA2B-DNAH5 fusion protein: DNAH5 C-terminal portion was fused to TRA2B N-terminal part to form a new fusion protein. (Image provided by Dr. JI Hongbin)
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences