Studies of Invadopodia Formation in Ewing sarcoma

Background

Metastatic cells are notoriously resilient and adaptive, which is why understanding how tumor cells adapt to stress will provide critical insights into how Ewing sarcoma cells become invasive. The project will specifically dissect how lack of oxygen and growth factors induce Ewing sarcoma cells to form new cell structures, termed invadopodia, that promote invasion and metastasis. Invadopodia are very complex cellular structures whose formation is tightly controlled by the coordinated activity of numerous proteins in the cell. Preliminary studies have identified that two key proteins that are involved in invadopodia formation change their activity in Ewing sarcoma cells under conditions of stress.

Project Goal

I will test whether interference with these proteins (called SRC and caldesmon) can block the creation of invadopodia and block cell invasion. These studies will be highly informative as there is FDA-approved drug, dasatinib that can be used to block SRC activation and invadopodia formation. Demonstration that blocking SRC can block the invasive properties of Ewing sarcoma cells under conditions of stress will provide key data to support further investigating this approach for targeted anti-metastatic therapy.