Gadd45a inhibits cell migration and invasion by altering the global RNA expression

Abstract

Gadd45a, the first well-defined p53 downstream gene, can be induced by multiple DNA-damaging agents, which plays important roles in the control of cell cycle checkpoint, DNA repair process and signaling transduction. Our previous findings suggested that Gadd45a maintains cell-cell adhesion and cell contact inhibition. However, little is known about how Gadd45a participates in the suppression of malignancy in human cancer cells. To examine the functions of Gadd45a in cell invasion and metastasis, we performed the adhesion, wound-healing and transwell assays in Gadd45a^+/+ and Gadd45a^−/− MEF cell lines. We found the adhesion, migration and invasive abilities were much higher in Gadd45a deficient cells. We furthermore applied high-throughput cDNA microarray analysis and bioinformatics analysis to analyze the mechanisms of Gadd45a gene in invasion and metastasis. Compared with the Gadd45a wild type cells, the Gadd45a deficient cells showed a wide range of transcripts alterations. The altered gene pathways were predicted by the MAS software, which indicated focal adhesion,cell communication,ECM-receptor interaction as the three main pathways. Real-time PCR was employed to validate the differentially expressed genes. Interestingly, we figured out that the deregulations of these genes are caused neither by genomic aberrations nor methylation status. These findings provided a novel insight that Gadd45a may involve in tumor progression by regulating related genes expressions.

Keywords: :

• Gadd45a
• adhesion
• migration
• invasion
• microarray
• methylation

Disclosure of Potential Conflicts of Interest

The authors declare there are no conflicts of interest.

Acknowledgments

The authors would like to thank Professor Albert J. Fornace and M. Christine Hollander for kindly giving us the Gadd45a^+/+ and Gadd45a^−/− (MEFs) cell lines.

This work is supported by the funding from the 973 National Key Fundamental Research Program of China (2009CB521801) and the National Natural Science Foundation of China (81021061).