Vascular endothelial growth factors (VEGFs) consist of five molecules (VEGFA through D as well as placental growth factor) which are crucial for regulating key cellular and tissue functions. The role of VEGF and its intracellular signaling and downstream molecular pathways have been thoroughly studied. Activation of VEGF signal transduction can be initiated by the molecules’ binding to two classes of transmembrane receptors: (1) the VEGF tyrosine kinase receptors (VEGF receptors 1 through 3) and (2) the neuropilins (NRP1 and 2). The involvement of Rho GTPases in modulating VEGFA signaling in both cancer cells and endothelial cells has also been well established. Additionally, different isoforms of Rho GTPases, namely, RhoA, RhoC, and RhoG, have been shown to regulate VEGF expression as well as blood vessel formation. This review article will explore how Rho GTPases modulate VEGF signaling and the consequences of such interaction on cancer progression.

Background Coronary Artery Disease (CAD) is the narrowing or blockage of the coronary arteries. It is closely associated with numerous genetics and environmental factors that have been extensively evaluated in various populations. In recent studies, severe phenotypes have been strongly linked to genetic risk factors. Methods This study investigated the association of clinical, demographic, and genetic factors with severe coronary artery stenosis phenotypes in our population composed of 1734 individuals with severe coronary stenosis (≥ 50% in coronary vessels) and comparing them to 757 controls with no evidence of stenosis on angiography. We performed generalized linear model (GLM) genome-wide association studies to evaluate three stratification models and their associations to characteristics of the clinical disease. In model 1, patients were not stratified. In model 2, patients were stratified based on presence or absence of CAD family history (FxCAD). In model 3, patients were stratified by young age of CAD onset. Results Eight SNPs (single nucleotide polymorphism) were significantly associated with severe CAD phenotypes in the various models $$\left( {p < 5 \times 10^{ - 7} } \right)$$ p < 5 × 10 - 7 , four of these SNPs were associated with severe CAD and the four others were specifically significant for young CAD patients. While these SNPs were not previously reported for association with CAD, six of them are present in genes that have already been linked to coronary disease. Conclusion In conclusion, this study presents new genetic factors associated with severe stenosis and highlights different risk factors associated with a young age at diagnosis of CAD.

Glioblastoma multiforme (GBM), also referred to as glioblastoma is a rapidly dividing glioma that develops from astrocytes and oligodendrocytes (glial cells that nourish the brain). GBM can also be classified as a grade IV astrocytoma, which represents the most invasive, rapidly growing, and metastatic type of glial tumors. Our lab has been primarily interested in identifying and studying pathways relevant to the progression of this disease through which we recently determined that hypoxia and EGF stimulation contribute to VEGF expression via the differential regulation of the PI3K/Rho-GTPase and MAPK signaling pathways. Palladin is a relatively novel actin-associated phosphoprotein that has been reported to be implicated in a variety of cancers such as pancreatic adenocarcinoma and ductal carcinoma of the breast. It has also been reportedly involved in the development of invadopodia, dorsal ruffles, podosomes, focal adhesions, and has been shown to be involved in regulating the expression of the Rho-GTPases, Cdc42 and Rac1. More recently, palladin has been shown to alter actin dynamics in podocytes as well as replace the Arp2/3 complex during Listeria infections, contributing to the assembly of actin-based structures. In this study, we used a palladin knockdown model in order to assess invadopodia formation in glioblastoma cell line U87. The results show an increase in invadopodia as seen by TKS4 and TKS5 staining as well as a decrease in Cdc42 activity following palladin knockdown. We have also been able to demonstrate a novel role for palladin in the expression of Rac1. This study serves to characterize palladin within the context of invadopodia formation and as such we have been able to identify potential crosstalk between palladin and Rho GTPases such as Cdc42 and Rac1.