Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown.
Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesis and tumour-cell invasion.
The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor.
Expression of the Ets2DBD almost completely blocked PPC-1 cell invasion through Matrigel, whereas over-expression of full-length Ets2 did not inhibit invasion.
In HCC, the ets-2 expression level was significantly lower in cases with advanced stage (p=0.0085), large size (p=0.0441), high proliferating activity (p<0.0001), poor differentiation (p=0.0005), the presence of portal invasion (p=0.0009) and intrahepatic metastasis (p=0.0236) and shorter disease-free survival (p=0.0372).
Our data show that stable expression of the mutant Ets2 in BT20 cells completely inhibits the formation of soft agar colonies and abolishes the CSF-1-stimulated invasion of these cells through a barrier of reconstituted basement membrane (Matrigel).