Tumor invasion as dysregulated cell motility

Investigations across a range of disciplines over the past decade have brou ght the study of cell motility and its role in invasion to an exciting thre shold. The biophysical forces proximally involved in generating cell locomo tion, as well as the underlying signaling and genomic regulatory processes, are gradually becoming elucidated. We now appreciate the intricacies of th e many cellular and extracellular events that modulate cell migration. This has enabled the demonstration of a causal role of cell motility in tumor p rogression, with various points of 'dysregulation' of motility being respon sible for promoting invasion. In this paper, we describe key fundamental pr inciples governing cell motility and branch out too describe the essence of the data that describes these principles. It has become evident that many proposed models may indeed be converging into a tightly-woven tapestry of c oordinated events which employ various growth factors and their receptors, adhesion receptors (integrins), downstream molecules, cytoskeletal componen ts, and altered genomic regulation to accomplish cell motility. Tumor invas ion occurs in response to dysregulation of many of these modulatory points; specific examples include increased signaling from the EGF receptor and th rough PLC gamma, altered localization and expression of integrins, changes in actin modifying proteins and increased transcriptions from specific prom oter sites. This diversity of alterations all leading to tumor invasion poi nt to the difficulty of correcting causal events leading to tumor invasion and rather suggest that the underlying common processes required for motili ty be targeted for therapeutic intervention.