Astrocyte Elevated Gene-1 Increases Invasiveness of NSCLC Through Up-Regulating MMP7

• Main Authors: Ren Zhu, Ye Tian
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2015-09-01
• Series: Cellular Physiology and Biochemistry
• Subjects: ERK/MAPK signaling pathway; Non-small cell lung cancer (NSCLC); Astrocyte elevated gene-1 (AEG-1); Matrix metalloproteinase 7 (MMP7); Metastases
• Online Access: http://www.karger.com/Article/FullText/430242
• ISSN: 1015-8987; 1421-9778

Background/Aims: The aggressive manner of non-small cell lung cancer (NSCLC) cells accounts for the majority of the lethality of the disease. Recently, increased astrocyte elevated gene-1 (AEG-1) levels have been shown to closely correlate with poor prognosis of NSCLC, whereas the underlying mechanisms are not clear. Methods: We examined the AEG-1 and matrix metalloproteinase 7 (MMP7) levels in NSCLC tissues, compared to the paired adjacent non-tumor lung tissue. We modulated AEG-1 levels in NSCLC cells, and examined its effects on MMP7 levels by RT-qPCR, on cellular protein by Western blot, and on secreted protein by ELISA. We also examined the cell invasiveness in AEG-1-modified NSCLC cells in a transwell cell migration assay. We used specific signal pathway inhibitors to treat AEG-1-modified NSCLC cells and examined its effects on MMP7. Results: AEG-1 and MMP7 levels were both significantly increased in NSCLC tissues, compared to the paired adjacent non-tumor lung tissue. The AEG-1 and MMP7 levels were strongly correlated. Overexpression of AEG-1 in NSCLC cells significantly increased MMP7 levels and cell invasiveness, while AEG-1 depletion in NSCLC cells significantly decreased MMP7 levels and cell invasiveness. Application of a specific MAPK-p42/p44 inhibitor, but not application of specific inhibitors for MAPK-p38, PI3k/Akt, or JNK signaling pathways, to AEG-1-overexpressing NSCLC cells substantially abolished the AEG-1-mediated MMP7 up regulation. Conclusion: AEG-1 promotes NSCLC cell invasiveness through MAPK-p42/p44-dependent activation of MMP7.