SPANX (Sperm protein associated with the nucleus, X-linked) gene family has been found higher expression in many cancers, such as testicular germ tumor, melanoma, glioblastoma and hematologic malignancies. However, in our previous study, the gene expression array analysis showed that the expression of SPANX family member A1 (SPANXA1) was higher in lower invasive lung cancer cells, CL 1-0, than in higher invasive cells, CL 1-5. Real-time PCR was used to confirm that mRNA expression of SPANXA1 was 8 times higher in CL 1-0 than CL 1-5. In vitro assays showed that migration and invasion abilities of CL 1-5 stable transfectants were decreased in a dose-depended manner. Interestingly, cell morphology dramatically changed from mesenchymal-like to epithelial-like in CL 1-5 SPANXA1 stable transfectants, which was consistent to its decreased invasive ability in vitro. Therefore, we demonstrated metastasis ability of CL 1-5 SPANXA1 stable transfectants would be down-regulated in vivo, which was performed in mouse metastasis model by tail-vein injection. Next, we set up CL 1-0 lentiviral-base shRNA knockdown clones, and the cell mobility and invasion ability were increased. Because SPANXA1 could induce the cell morphology change, we evaluate the effect of SPANXA1 on the expression of EMT markers. We found up-regulation of E-cadherin, an epithelial marker, and down-regulation of vimentin and N-cadherin, which were known as mesenchymal markers in presence of SPANXA1. Finally, to identify the underlying mechanism of SPANXA1, we carried out gene expression array and 3 of top 10 pathways are EMT-related. Furthermore, quantitative RT-PCR validation showed WNT pathway is involved in SPANXA1-repressed metastasis indicated that SPANXA1 might provide a new treatment in lung cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3990. doi:1538-7445.AM2012-3990