SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma

// Yi-Jing Hsiao 1 , Kang-Yi Su 1, 2, 3 , Yi-Chiung Hsu 4 , Gee-Chen Chang 5, 6 , Jin-Shing Chen 7 , Hsuan-Yu Chen 2, 4 , Qi-Sheng Hong 1 , Shih-Chun Hsu 1 , Po-Hsiang Kang 1 , Chia-Ying Hsu 1 , Bing-Ching Ho 1 , Tsung-Hui Yang 1 , Chia-Yu Wang 1 , Yuh-Shan Jou 8 , Pan-Chyr Yang 2, 8, 9 , Sung-Liang Yu 1, 2, 3, 10, 11, 12 1 Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan 2 Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan 3 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 4 Institute of Statistical Science, Academia Sinica, Taipei, Taiwan 5 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 6 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 7 Division of Thoracic Surgery and Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 8 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 9 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 10 Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan 11 Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan 12 Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan Correspondence to: Sung-Liang Yu, email: slyu@ntu.edu.tw Keywords: SPANX family, AP-1, SLUG, E-cadherin, metastasis Received: January 07, 2016 Accepted: June 01, 2016 Published: June 15, 2016 ABSTRACT SPANXA (Sperm Protein Associated with the Nucleus on the X-chromosome, family members A1/A2) acts as a cancer-testis antigen expressed in normal testes, but dysregulated in various tumors. We found that SPANXA is highly expressed in low-invasive CL1-0 cells compared with isogenous high-invasive CL1-5 cells. SPANXA was preferably expressed in tumor tissues and associated with the prolonged survival of lung adenocarcinomas. SPANXA suppressed the invasion and metastasis of lung cancer cells in vitro and in vivo . By the expression microarray and pathway analysis, we found that the SPANXA-altered genes were enriched in the epithelial–mesenchymal transition (EMT) pathway. SPANXA reduced SNAI2 expression resulted in up-regulating E-cadherin . c-JUN acts as the positive-regulator of EMT. Silencing SPANXA increased c-JUN mRNA expression and blockage of c-JUN led to SNAI2 down-regulation. Our results clearly characterized SPANXA as an EMT inhibitor by suppressing c-JUN-SNAI2 axis in lung adenocarcinoma.