Implication of STAT3 Signaling in Human Colonic Cancer Cells during Intestinal Trefoil Factor 3 (TFF3) – and Vascular Endothelial Growth Factor–Mediated Cellular Invasion and Tumor Growth

摘要: Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types human tumors has been classified as an oncogene. In the present study, we investigated contribution STAT3s to proinvasive activity trefoil factors (TFF) vascular endothelial growth factor (VEGF) colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal peptide (TFF3) VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr(705) phosphorylation both STAT3alpha STAT3beta isoforms. Blockade by STAT3beta, depletion STAT3alpha/beta isoforms RNA interference, pharmacologic inhibition cucurbitacin inhibitory abrogates TFF- VEGF-induced cellular invasion reduces tumor xenografts athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression down-regulates receptors Flt-1, neuropilins 1 2, inhibitor binding/differentiation (Id-2) product involved neoplastic transformation. Taken together, our data suggest TFF3 essential angiogenesis regulator VEGF(165) exert potent cells. We also validate new therapeutic strategies targeting inhibitors interference for treatment patients.