Targeting the Function of Ezrin in Rhabdomyosarcoma
Rhabdomyosarcomas are a rare but aggressive type of cancer in children and adolescents. There are approximately 350 new diagnoses of childhood RMS in the United States per year. The outcomes for high-risk patients with this disease have not significantly improved in the last several decades and survival of metastatic or relapsed disease remains extremely poor. In rhabdomyosarcoma the tumor cells resemble dividing muscle cells.
We will investigate a protein called Ezrin whose expression is increased in highly metastatic rhabdomyosarcomas. Because the activity of Ezrin depends on its phosphorylation at a specific amino acid residue, we will study the relationship between phosphorylated Ezrin and rhabdomyosarcoma metastasis and investigate if ablating Ezrin phosphorylation restricts the spread of the disease.
We will address the following questions:
(1) Does decreasing Ezrin phosphorylation kill rhabdomyosarcoma cells and make them less metastatic?
(2) Do high levels of phosphorylated Ezrin mark certain types of rhabdomyosarcoma?
The potential impact of this research includes more accurate diagnosis of patients with rhabdomyosarcoma, a better understanding of the role of phosphorylated Ezrin in rhabdomyosarcoma metastasis, and future development of better drugs targeting the function of Ezrin.