Genome-wide analysis of cancer cell-derived Foxp3 target genes in human tongue squamous cell carcinoma cells.

ABSTRACT

The forkhead transcription factor Foxp3 is essential for differentiation and activation of regulatory T cells (Tregs), and used to be regarded as specific transcription factor of Tregs. In recent years, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained great interest, but its function and molecular mechanisms remain incompletely understood. In the present study, we detected dynamic nuclear translocation of Foxp3 in TSCC cells using immunofluorescent staining. Then we performed a genome-wide analysis of Foxp3 in TSCC cells using a combination of ChIP-on-chip and whole-genome microarray assays. We also compared Foxp3 biding sites in TSCC cells with the known binding sites in human Tregs to show the differences in transcriptional regulation profile. Results indicate that Foxp3 in TSCC cells has distinct biological functions compared with that in Tregs. Cancer cell-derived Foxp3 directly regulates the transcription of genes that affect certain internal biological processes of TSCC cells, and indirectly influences the extracellular microenvironment. This study reveals the relationship between direct and indirect targets genes of Foxp3 in TSCC cells and provide molecular basis of cancer cell-derived Foxp3 function.