Rac GTPases in Hematological Malignancies

Abstract

Emerging evidence suggests that crosstalk between hematologic tumor cells and the tumor microenvironment contributes to leukemia and lymphoma cell migration, survival, and proliferation. The supportive tumor cell-microenvironment interactions and the resulting cellular processes require adaptations and modulations of the cytoskeleton. The Rac subfamily of the Rho family GTPases includes key regulators of the cytoskeleton, with essential functions in both normal and transformed leukocytes. Rac proteins function downstream of receptor tyrosine kinases, chemokine receptors, and integrins, orchestrating a multitude of signals arising from the microenvironment. As such, it is not surprising that deregulation of Rac expression and activation plays a role in the development and progression of hematological malignancies. In this review, we will give an overview of the specific contribution of the deregulation of Rac GTPases in hematologic malignancies.

Keywords: Rac GTPases; cancer; leukemia; lymphoma; microenvironment; migration; proliferation; survival.

Figure 1

Schematic illustration of Rac signaling pathways contributing to adhesion, migration and engraftment, survival, and proliferation of hematological tumor cells. Depicted are upstream and downstream molecules and interaction partners of Rac GTPases that have been found in the different types of leukemia and lymphoma. Rac activating pathways are represented by blue arrows, direct or indirect activation downstream of Rac are represented by black arrows, direct interactions are marked by double black lines, and blocking processes are indicated by red bar-headed lines.