ETS transcription factors and targets in tumour invasion, angiogenesis and bone metastasis

Abstract

The ETS gene family encodes unique transcription regulators that have a common ETS DNA binding domain. At least 25 distinct ETS related genes have been isolated from various species. The ETS family transcription factors are known to regulate genetic programs essential for differentiation and development processes and play diverse roles in a number of biological processes such as organogenesis and tissue remodelling during murine development, hematopoiesis, B-cell development, activation of T-cells and signal transduction, as well as osteogenesis, osteoblast differentiation and extracellular matrix mineralization. Based on the observation of overexpression of ETS related genes in various primary and metastatic tumors, their utility as potential therapeutic targets has been suggested. Antisense oligonucleotides, transdominant, and dominant-negative mutants have been exploited to target and inhibit ETS gene expression selectively. These ETS-targeted studies are being pursued to assess their antitumour effect, and hold the potential that such specific ETS-targeted inhibitors may become a viable option for cancer therapy. Collectively, these studies also demonstrate that Ets factors can regulate multiple aspects of the malignant phenotype of many tumor cells in particular neoangiogenesis and extracellular matrix-regulated (ECM-regulated) cell proliferation, motility and invasiveness.