Emerging roles of PDGF-D signaling pathway in tumor development and progression

Abstract

Platelet-derived growth factor-D (PDGF-D) can regulate many cellular processes, including cell proliferation, apoptosis, transformation, migration, invasion, angiogenesis and metastasis. Therefore PDGF-D signaling has been considered to be important in human malignancies, and thus PDGF-D signaling may represent a novel therapeutic target, and as such suggests that the development of agents that will target PDGF-D signaling is likely to have a significant therapeutic impact on human cancers. This mini-review describes the mechanisms of signal transduction associated with PDGF-D signaling to support the role of PDGF-D in the carcinogenesis. Moreover, we summarize data on several PDGF-D inhibitors especially naturally occurring "chemopreventive agent" such an indole compound, which we believe could serve as a novel agent for the prevention of tumor progression and/or treatment of human malignancies by targeted inactivation of PDGF-D signaling.

Figure-1

A; Schematic drawing of the four PDGF proteins (PDGF-A, B, C, D). B; Demonstrates the PDGF-PDGFR interactions.

Figure-2

Diagram of PDGF-D cross-talks with other pathways. ERK: extracellular signal-regulated kinase; IL-1β: proinflammatory cytokine interleukin-1β; MAPK: mitogen-activated proteinkinase; MMPs: matrix metalloproteinases; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor-κB; PI3K: phosphatidylinositol 3-kinase; ROS: reactive oxygen species; uPA: urokinase-type plasminogen activator; VEGF: vascular endothelial growth factor. EMT: epithelial-mesenchymal transition.