We study the signal transduction mechanisms that promote cell migration of cancer cells and those of the tumor stroma. Like endothelial cells that contribute to tumor growth and metastatic dissemination. Signaling proteins that promote morphological adjustments required for invasion and metastasis of cancer cells, either stimulated by chemotactic factors from the tumor microenvironment or as effectors of oncogenic proteins, are potential therapeutic targets. Their identification and characterization set the basis for drug discovery to explore new strategies to treat cancer.
We focus on the molecular mechanisms that activate RhoGEFs, which are sophisticated multidomain proteins that integrate signaling cascades stimulated by chemotactic receptors. We study RhoGEFs as possible effectors of oncogenic proteins that drive cancer cell dissemination and activation of tumor stromal cells. RhoGEFs (guanine nucleotide exchange factors for Rho family GTPases) are controlled by dynamic interaction with other signaling proteins, post-translational modifications, and second messengers. They constitute signaling hubs that result in localized activation of Rho GTPases, which are molecular switches that, once turned on, trigger the morphological adjustments required for cell movement.