When scientists obstructed a protein called ETV6 in Ewing sarcoma cancer cells (left), they reverted back to typical connective tissue cells (right), which drastically altered their size, shape, and behavior. Credit: Vakoc lab/Cold Spring Harbor Laboratory
When their experiments revealed that Ewing sarcoma cells seem distinctively dependent on this protein, Vakoc and his coworkers became excited about ETV6. “This protein is present in all cells. When you trouble the protein, most typical cells do not care,” he states. “The process by which the sarcoma types turns this ETV6 particle– this reasonably harmless, safe protein that isnt doing quite– into something thats now controlling a life-death decision of the tumor cell.”
When Gao obstructed ETV6 in Ewing sarcoma cells grown in the lab, she witnessed a remarkable change. “The sarcoma cell reverts back into being a typical cell again,” she says. “The shape of the cell changes.
Vakoc and Gao hope other researchers will use what theyve found out to begin checking out prospective therapies for Ewing sarcoma that work by turning off ETV6. They say their biochemical analyses, which identify specific areas in the ETV6 protein that are crucial to its function in cancer cells, could help guide drug advancement. Since their experiments have revealed that the majority of cells are unaffected by the loss of ETV6 activity, they are positive that such a drug may be able to remove cancer cells while triggering few, if any, side effects.
Recommendation: “ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation” by Yuan Gao, Xue-Yan He, Xiaoli S. Wu, Yu-Han Huang, Shushan Toneyan, Taehoon Ha, Jonathan J. Ipsaro, Peter K. Koo, Leemor Joshua-Tor, Kelly M. Bailey, Mikala Egeblad and Christopher R. Vakoc, 19 January 2023, Nature Cell Biology.DOI: 10.1038/ s41556-022-01060-1.
The study was funded by the National Cancer Institute, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, Friends of T.J. Foundation, the Christina Renna Foundation, the Michelle Paternoster Foundation, the William J. Riley Foundation, and the Howard Hughes Medical Institute.
Vakoc and his associates ended up being excited about ETV6 when their experiments revealed that Ewing sarcoma cells seem uniquely reliant on this protein. “The process by which the sarcoma kinds turns this ETV6 particle– this reasonably innocuous, safe protein that isnt doing very much– into something thats now managing a life-death decision of the growth cell.”
When Gao blocked ETV6 in Ewing sarcoma cells grown in the laboratory, she witnessed a dramatic improvement. “The sarcoma cell reverts back into being a regular cell once again,” she states. Since their experiments have revealed that many cells are untouched by the loss of ETV6 activity, they are positive that such a drug may be able to get rid of cancer cells while triggering couple of, if any, side results.
Scientists found targeting a protein called ETV6 can turn Ewing sarcoma cancer cells back to normal-looking and -acting connective tissue cells, as seen above. Credit: Vakoc lab/Cold Spring Harbor Laboratory
Researchers at Cold Spring Harbor Laboratory (CSHL) have identified a new drug target for Ewing sarcoma, an unusual kind of cancer usually identified in kids and young grownups. Their experiments reveal that the cells responsible for this cancer can be efficiently reprogrammed with the flick of a genetic switch.
Shutting down a single protein requires the cancer cells to take on a brand-new identity and behave like regular connective tissue cells, a dramatic modification that control their growth. This discovery suggests researchers might be able to stop Ewing sarcoma by establishing a drug that blocks the protein understood as ETV6.
Ewing sarcoma triggers tumors to grow in bones or the soft tissues surrounding them. Even for clients with positive outcomes, treating Ewing sarcoma often triggers poisonous side results.