Abstract

It is worth mentioning that large body of experimental evidence interconnects the deregulation of specific platelet-derived growth factor (PDGF) functions to cellular transformation, yet complete picture of determinants of molecular mechanisms through which PDGF contributes to tumorigenesis remain indefinable. In this review, we have summarized current comprehension concerning PDGF functions, and attempted to understand its multifaceted and contradictory activities in the perspective of both normal cellular  homeostasis and molecular disorders. Furthermore, PDGF is tightly buffered at multiple levels by downstream components and effectors, which have turned this linear signaling pathway into an integrated one. In support of this notion, PDGF and its downstream components in turn cross-talk with a number of other pathways, consequently leading to an intricate network of signals that may have derailed activities when perturbed. Here, we evaluate the current status of the PDGF transduction cascade with particular emphasis on the most current data on targets and regulation of the PDGF axis. We also bring to limelight, molecular details of PDGF signal transduction cascade, endocytosis and membrane trafficking, as well as interactions with the actin cytoskeleton which may add to the recently appraised multifunctionality of PDGF. This provides novel therapeutic implications based on the targeted modulation of PDGF-cross-talking signals with minimal off target effects.

Key words: Platelet-derived growth factor, cancer, cellular transformation.