PT - JOURNAL ARTICLE AU - SEONG-HOON YUN AU - SANG-HEUM HAN AU - JOO-IN PARK TI - COUP-TFII Knock-down Promotes Proliferation and Invasion in Colorectal Cancer Cells <em>via</em> Activation of Akt Pathway and Up-regulation of FOXC1 AID - 10.21873/anticanres.13939 DP - 2020 Jan 01 TA - Anticancer Research PG - 177--190 VI - 40 IP - 1 4099 - http://ar.iiarjournals.org/content/40/1/177.short 4100 - http://ar.iiarjournals.org/content/40/1/177.full SO - Anticancer Res2020 Jan 01; 40 AB - Background/Aim: The chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) regulates cancer cell proliferation and invasion via complex molecular mechanisms. We aimed to investigate whether COUP-TFII modulates proliferation and invasion of the colorectal adenocarcinoma cell line HT-29. Materials and Methods: HT-29 cells were stably tranfected with COUP-TFII shRNA plasmid to knock-down COUP-TFII (COUP-TFII shRNA-HT-29 cells). Cell proliferation, colony formation assay, invasion assay, microarray assays and western blot analyses were performed. Results: Cell proliferation and invasion were significantly enhanced in COUP-TFII shRNA-HT-29 cells. The protein levels of forkhead box C1 (FOXC1), p-Akt, p-glycogen synthase kinase-3β (p-GSK-3β), and β-catenin, which are known to be involved in cell proliferation and invasion, were significantly increased in COUP-TFII shRNA-HT-29 cells. Akt inhibitor IV and dominant negative (DN)-Akt expression vector transfection reversed the increased proliferation and invasion, which was accompanied by decreased protein levels of p-Akt, p-GSK-3β, β-catenin and FOXC1. Conclusion: COUP-TFII knock-down promoted proliferation and invasion via activation of Akt/GSK-3β/β-catenin and up-regulation of FOXC1. Further studies on the molecular mechanism of interaction between β-catenin and FOXC1 expression may reveal novel target molecules for metastatic colorectal cancer therapy.