Towards elucidation of functional molecular signatures of the adhesive-migratory phenotype of malignant cells.

Over the years, malignant transformation has been investigated on multiple levels, ranging from clinical pathology to the underlying molecular mechanisms. In "zooming in" on this process, cancer biologists have focused their attention on the molecular and cellular manifestations of the "transformed phenotype", including the genomic instability of cancer cells, their deregulated transcriptional activity, their aberrant morphology and dynamics, and the altered signaling networks activated in them. Attempts to elucidate the mechanisms underlying malignant and metastatic transformation are primarily motivated by the desire to identify specific molecules and signaling pathways that can serve as targets for novel therapies. In recent years, such studies were reinforced by major technological and conceptual developments: novel and powerful tools for genomic and proteomic analysis have been developed, and advanced computational approaches offer "systems-level" integration of rich and complex biological datasets into meaningful functional networks. In this article, we consider the current and potential impact of these new experimental approaches and, in particular, the recent progress made in quantitative proteomics, to elucidate the mechanisms underlying the "transformed phenotype". We will primarily focus on the adhesion and migration of cancer cells, and their relationships to the deregulated growth, metastatic dissemination, and anchorage independence associated with malignant transformation.