Cortactin and its hematopoietic homolog, HS1, are actin-binding proteins that regulate several cellular functions. In T cells, HS1 is recruited to the immunological synapse where it is essential for F-actin stabilization, Ca++ influx, NFAT- and NF-κB-mediated signaling and chemotaxis. On the other hand, cortactin has long been considered absent in T cells. Recent studies have shown that cortactin is expressed in T cells and is recruited to the immunological synapse between Jurkat and Nalm-6 cells. However, the physiological relevance of its presence here remains elusive.
On the other hand, cortactin has been found highly expressed in different models of T-cell acute lymphoblastic leukemia (T-ALL). T-cell acute lymphoblastic leukemia has been historically considered as an aggressive disease among lymphoblastic leukemias in children. Previous work from our team showed that cortactin is overexpressed in B-cell acute lymphoblastic leukemia, and its presence associated with extramedullar infiltration and failure of steroid treatment. However, it is still unclear whether higher expression of cortactin is related to the aggressiveness observed during T-ALL. The main objective of my work is to elucidate the physiological relevance of cortactin for the activation of healthy CD4+ T cells and its contribution in the pathophysiology of T-cell acute lymphoblastic leukemia.