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.
Highlights
Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is the major subtype, accounting for 50% of the incidence of non-small cell lung cancer (NSCLC) [1, 2]
SPANXA is upregulated in tumor tissues and associated with prolonged survival in lung adenocarcinoma patients
We assessed whether the SPANXA expression is associated with survival of lung adenocarcinoma patients
Summary
Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is the major subtype, accounting for 50% of the incidence of non-small cell lung cancer (NSCLC) [1, 2]. We established a series of lung cancer cell lines CL1-0, CL1-1, CL1-2 and CL1-5, with various malignancies and invasiveness [9] Using this cell line model and microarray analysis, we identified several invasion-related genes, and characterized their roles in metastasis [7, 10,11,12]. SPANXA/D proteins have been found in various tumors, such as melanoma, bladder carcinomas, myeloma, head and neck squamous cell carcinoma (HNSCC), as well as colorectal and prostate cancers [14, 20,21,22,23] Their roles in spermiogenesis and cancer progression are largely unknown. SPANXA1 and SPANXA2 encode the same mRNA and protein, and the biological functions remain to explore
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