PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis

Ewing's Sarcoma family tumors (ESFT) are characterized by a translocation t(11: 22) forming an aberrant transcription factor EWS-FLI1. Protein tyrosine phosphatase L1 (PTPL1) was identified as a gene upregulated by EWS-FLI1 in transfected cells by microarray. Our results show that PTPL1 is a transcriptional target of EWS-FLI1 both by chromatin immunoprecipitation and promoter activation studies. We demonstrate that PTPL1 is highly expressed in ESFT cells and patient tumors compared with normal tissues, witha trend towards higher expression in metastatic versus primary tumors. Reduction of PTPL1 protein in ESFT cells correlated witha significant reduction in both monolayer and soft-agar cell growth. In addition, these PTPL1-reduced cells were more sensitive to etoposide-induced apoptosis than the controls. We therefore report a novel transcriptional activation of a phosphatase involved in the oncogenesis of ESFT. Increasing interest in specific phosphatase inhibitors would allow PTPL1 to be evaluated as a therapeutic target in ESFT.