Frank van Leeuwen
224 Research Laboratory of Pediatric Oncology
P.O. BOX 9101
6500 HB Nijmegen
Mechanical forces play an important role in the growth, maintenance and function of tissues and organ systems. External forces applied to the cell are sensed at cell-matrix adhesions through integrins that connect the extracellular matrix to the underlying actomyosin cytoskeleton. Conversely, actomyosin contractility generated intracellularly affects cell adhesion strength and matrix rigidity. This balance of forces is known as tensional homeostasis.
Our efforts are directed at defining signalling pathways and molecular mechanisms that regulate tensional homeostasis by affecting actomyosin-based contraction. Moreover, we would like to understand how deregulation of these pathways contributes to tumor cell progression, invasion and metastasis. Previously, we established that the small GTPases Rac1 and Rho A oppositely control actomyosin contractility, affecting cell adhesion, migration and spreading. At present, we are investigating a role for the channel-kinase TRPM7, both a cation channel and a Myosin II heavy chain kinase, in regulating cytoskeletal tension and cell adhesion. For these studies, we use a multidisciplinary approach combining biochemistry, cell biology, molecular biology, proteomics and cell physiology.