Cell polarity is a fundamental characteristic of many cell types essential for their function. One of the protein complexes responsible for development and maintenance of cell polarisation is the Scrib/Dlg/Lgl-polarity module. Furthermore, the proteins building this complex act as tumour suppressors. Endothelial cells also show a certain polarisation and their proliferation and migration are important steps during the angiogenic process. However, little is known regarding a possible expression of the Scrib/Dlg/Lgl-module in endothelial cells. We studied the expression of the Scrib-module and determined its role in angiogenesis-associated processes. Analysing mRNA by RT-PCR, expression of Scrib, Dlg5 and Lgl1 were detected in human umbilical vein endothelial cells (HUVEC) at a similar level as in different epithelial cell lines. Also Scrib protein was found to be expressed in HUVEC in an amount comparable to that in epithelial cells. Overexpression of Scrib in HUVEC attenuated tube formation in the Matrigel assay whereas downregulation of the protein by RNAi, had a stimulatory effect in this assay. In contrast, Scrib RNAi inhibited endothelial sprouting in the spheroid assay in collagen gels. This combination is indicative towards an induction of an endothelial "stalk cell" phenotype by Scrib RNAi which may result from an activation of the Notch signalling pathway. Indeed, preliminary results from luciferase reporter gene assays demonstrated increased activation of the Notch pathway after downregulation of Scrib. Additionally, overexpression of Scrib diminished the Dll4- induced activation of the Notch reporter construct. In conclusion, we were able to demonstrate that the polarity protein Scrib represents a new endothelial protein regulating the angiogenic process in vitro by modulation of the Notch signalling pathway. Since the results in the tube formation assays were independent of the angiogenic stimuli, a general role for Scrib during angiogenesis can be assumed.