A novel BMX variant promotes tumor cell growth and migration in lung adenocarcinoma

// Ye Wang 1, 2, 3 , Jufeng Xia 1, 2, 3 , Zhaoyuan Fang 1, 2, 3 , Fei Li 1, 2, 3 , Duo Li 1, 2, 3 , Zuoyun Wang 1, 2, 3 , Yan Feng 1, 2, 3 , Jian Zhang 1, 2, 3 , Haiquan Chen 6, 7 , Hongbin Ji 1, 2, 3, 5 , Hongyan Liu 1, 2, 3, 4 1 CAS Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China 2 CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China 3 Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China 4 Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China 5 School of Life Science and Technology, Shanghai Tech University, Shanghai, 200120, China 6 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China 7 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China Correspondence to: Hongyan Liu, email: hyliudycui@aliyun.com Hongbin Ji, email: hbji@sibcb.ac.cn Keywords: lung adenocarcinomas, BMXΔN, cell proliferation, migration, skipping variant Received: January 12, 2017 Accepted: March 22, 2017 Published: April 03, 2017 ABSTRACT The non-receptor tyrosine kinase BMX has been reported in several solid tumors. However, the alternative splicing of BMX and its clinical relevance in lung cancer remain to be elucidated. Exon1.0 array was used to identify a novel alternative splicing of BMX, BMXΔN , which was confirmed by rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. BMXΔN , resulting from exon skipping with excluding exon 1 to exon 8 of BMX gene, was found in 12% human lung adenocarcinoma specimens. BMXΔN is not found in paired pathologically normal lungs and positively correlated with EGFR mutation in lung adenocarcinomas. Moreover, BMXΔN increases cell proliferation, neoplastic transformation, and migratory property of human non-small cell lung cancer cells. The function of BMXΔN in lung cancer might be presumably due to enhanced ERK signaling.