ZIC2 promotes colorectal cancer growth and metastasis through the TGF-β signaling pathway

ZIC2 is involved in the tumor progression of many types of cancers. The role of ZIC2 in the metastasis of colorectal cancer and its mechanism are not yet clear. In this study, we found that high ZIC2 expression was not only associated with poor prognosis, relapse-free survival and advanced metastasis but was also an independent prognostic factor in colorectal cancer patients. Moreover, ZIC2 knockdown inhibited cell proliferation, migration and invasion, while the upregulation of ZIC2 had the opposite effect in vitro. ZIC2 overexpression induced TGF-β1 expression and increased Smad3 phosphorylation. The carcinogenic effects of elevated ZIC2 expression can be eliminated by interfering with the TGF-β1 receptor with inhibitors. This further verified the promoting effect of ZIC2 on the TGF-β signaling pathway. In vivo experiments have also confirmed that ZIC2 can promote liver metastases of colorectal cancer. The results suggest that ZIC2 is associated with poor prognosis and relapse-free survival in colorectal cancer patients. Moreover, ZIC2 promoted colorectal cancer progression and metastasis by activating the TGF-β signaling pathway. Hence, ZIC2 is expected to be a new therapeutic and prognostic target for colorectal cancer in the future.