By establishing the metastatic model in severe combined immune deficiency (SCID) mice, we also demonstrated that overexpressing GPC5 suppressed LAC migration and accordingly alerted EMT related markers, which including up-regulated E-cadherin and down-regulated Vimentin in both lung and liver metastasis.
Irrespective of reduced proliferation and invasion found on in vitro cell assays, persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells possibly contributed to CLM development in mice implanted with IGFBP1-overexpressing SW480 cells (CLM occurrences: SW480/IGFBP1-transfected mice vs. SW480/vector- and SW480/ALDH1A1-transfected mice, 4/8 vs. 0/10, p = 0.023).
Ectopic expression of HNF4α upregulated E-cadherin and downregulated vimentin in vitro, and suppressed SW480 xenograft tumor growth and liver metastasis in vivo.
Moreover, a trend was shown toward preferentially developing liver metastasis and peritoneal dissemination in colorectal carcinomas with Vimentin methylation (p = 0.052 and p = 0.080, respectively).