Getting the Message

It is by now a truism that tumors require a nourishing supply of blood vessels to survive, but there remains a tantalizing mystery. The endothelial cells that compose blood vessels are bombarded by a multiplicity of signals—growth factors, hormones and other molecules. As Donald Ingber, the Judah Folkman professor of vascular biology in the Department of Pathology at HMS and Children’s Hospital Boston, and colleagues discovered 30 years ago, these signals include mechanical forces exerted by the extracellular matrix. How do cells make sense of the cacophony? In the Feb. 26 Nature, Akiko Mammoto, an HMS instructor in surgery at Children’s, working with Ingber and colleagues, describes a pathway that integrates mechanical signals with chemical cues from the microenvironment. The pathway, triggered by the Rho-inhibiting enzyme p190RhoGap, modulates the activities of two antagonistic transcription factors, TFII-I and GATA-2, which together govern the expression of the angiogenesis-promoting receptor VEGFR2.