SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma.
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.
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Yi-Jing
YJ
Hsiao
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.|Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Kang-Yi
KY
Su
Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Yi-Chiung
YC
Hsu
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Gee-Chen
GC
Chang
Division of Thoracic Surgery and Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Jin-Shing
JS
Chen
Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Hsuan-Yu
HY
Chen
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Qi-Sheng
QS
Hong
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Shih-Chun
SC
Hsu
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Po-Hsiang
PH
Kang
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chia-Ying
CY
Hsu
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Bing-Ching
BC
Ho
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Tsung-Hui
TH
Yang
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chia-Yu
CY
Wang
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Yuh-Shan
YS
Jou
Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Pan-Chyr
PC
Yang
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.|Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.|Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan.
Sung-Liang
SL
Yu
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; C000604408:SNAI2 protein, human; C414403:SPANXA1 protein, human; D000071250:Snail Family Transcription Factors
AP-1; E-cadherin; SLUG; SPANX family; metastasis