Growth factor networks in tumor progression and metastasis
Animals use a conserved and relatively small set of growth factors and signaling pathways to generate diverse biological function. These very same growth factors and signaling pathways are hijacked by cancer cells as they “diversify” to gain the biological function of tumor metastasis. We seek to understand the cellular and molecular events that define the metastatic “gain of function” of these cancer cells by identifying and defining the key molecules/growth factors that enable the cells to metastasize which includes the discrete steps of extravasation, tumor cell survival, angiogenesis and metastatic outgrowth. This involves but is not limited to delineating the assemblies of protein–protein, protein–DNA, and protein–ligand complexes formed in the cells. Our contributions to defining the context and roles of a subset of these molecules, of which Transforming Growth Factor beta (TGF-β) is the archetype, and the emerging therapeutic avenues based on our unique mechanistic studies will be presented.