During cell migration, the Rho GTPase proteins RhoA, Rac and Cdc42 regulate multiple processes such as dynamics of the actin cytoskeleton, cell-cell contacts as well as cell-substrate adhesion. In the complex process of cancer invasion Rho GTPases also control proteins involved in tumor cell dissemination such as matrix metalloproteinases. In order to understand such multifaceted signaling we are currently conducting three major approaches in the lab:

Localized protein activities

The diverse range of Rho functions requires that stimulatory signals are relayed to precise locations at specific time-points in order to activate Rho GTPases locally. We use fluorescence probes capable of detecting the activated Rho GTPase conformation in living cells, in order to dissect distinct signaling pathways. In particular, we focus on altered localized Rho activity when in vitro cancer cell scattering is stimulated by growth factors known to be involved in cancer invasion.

Role of upstream regulators

Guanine nucleotide exchange factors activate Rho proteins as response to stimulatory signals and by doing so translate such signals into specific cellular effects. Using contemporary cell-biological methods such as siRNA technology and confocal microscopy we assess the role of guanine-nucleotide exchange factors in cell migration and cancer cell dissemination.

Regulation of gene expression by Rho proteins

The expression of many genes is altered in cancer cells adopting an aggressive invasive behavior. We study the regulation of genes downstream of Rho protein signaling particularly involved in the reorganization of the extracellular matrix. To do so, we use a multidisciplinary strategy involving fluorescence imaging as well as gene-expression studies.