Oncotarget

Research Papers:

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

Yi-Jing Hsiao, Kang-Yi Su, Yi-Chiung Hsu, Gee-Chen Chang, Jin-Shing Chen, Hsuan-Yu Chen, Qi-Sheng Hong, Shih-Chun Hsu, Po-Hsiang Kang, Chia-Ying Hsu, Bing-Ching Ho, Tsung-Hui Yang, Chia-Yu Wang, Yuh-Shan Jou, Pan-Chyr Yang and Sung-Liang Yu _

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Oncotarget. 2016; 7:44417-44429. https://doi.org/10.18632/oncotarget.10088

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Abstract

Yi-Jing Hsiao1, Kang-Yi Su1,2,3, Yi-Chiung Hsu4, Gee-Chen Chang5,6, Jin-Shing Chen7, Hsuan-Yu Chen2,4, Qi-Sheng Hong1, Shih-Chun Hsu1, Po-Hsiang Kang1, Chia-Ying Hsu1, Bing-Ching Ho1, Tsung-Hui Yang1, Chia-Yu Wang1, Yuh-Shan Jou8, Pan-Chyr Yang2,8,9, Sung-Liang Yu1,2,3,10,11,12

1Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan

2Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

4Institute of Statistical Science, Academia Sinica, Taipei, Taiwan

5Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

6Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

7Division of Thoracic Surgery and Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

8Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

9Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

10Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan

11Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

12Institute 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.


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