RNA Helicase Promotes Growth of Ewing's Sarcoma

Cancer researchers have found that the activity of the oncogenic protein EWS-FLI1, which is present in Ewing's sarcoma tumor cells, was enhanced by that of an RNA helicase found to be highly expressed in Ewing's sarcoma cell lines and patients' tumors.

Ewing's sarcoma occurs most frequently in male teenagers. This cancer develops as the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11. The fused genes produce the EWS-FLI1 fusion protein, which is only found in Ewing's sarcoma tumors.

Investigators at Georgetown University (Washington, DC, USA) sought co-factor proteins that might modulate the activity of EWS-FLI1 in order to find a means of chemically blocking this interaction and thereby slowing or stopping tumor growth.

They reported in the June 1, 2006, issue of Cancer Research that EWS-FLI1 specifically binds an RNA helicase A (RHA) peptide fragment comprising amino acids 630 to 1020. RHA is a member of the DEXH box helicase family of proteins, and is an integral component of protein complexes that regulate transcription and splicing.

"Proteins are three-dimensional structures, and the space between EWS-FLI1 and the helicase might be targetable by a small molecule that keeps the proteins apart,” explained first author Dr. Jeffrey Toretsky, associate professor of oncology and pediatrics at Georgetown University. "It could render EWS-FLI1 harmless while not affecting its partnering helicase protein. Understanding the molecules EWS-FLI1 interacts with may provide insights into similar diseases. Very little work has been done to study the functional partners of these translocation proteins, and this study may offer a new research approach.”



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