ZIC2 accelerates growth and stemness in gastric cancer through the Wnt/β-catenin pathway

Abstract

In the digestive system, gastric cancer (GC) is one of the most usual pernicious tumors. Despite great improvement has been created in treatment, it is still the second major reason of cancer-relevant death. Thus, further researches are required to explicate the latent molecular mechanisms and look for novel biomarkers. ZIC2 has been confirmed to be a facilitator in diversified cancers. However, the particular regulatory of ZIC2 in GC needs further investigation. In this work, it was notarized that ZIC2 expression was up-regulated in GC, and ZIC2 knockdown weakened GC cell proliferation. Moreover, ZIC2 suppression retarded cell migration and invasion. Additionally, results from the spheroid formation assay and western blot revealed that ZIC2 silencing reduced cell stemness. Next, we discovered that ZIC2 inhibition restrain the Wnt/β-catenin pathway through modulating β-catenin, Axin, c-myc and MMP-7 expression. At last, it was uncovered that ZIC2 repression relieved tumor growth in vivo. In summary, ZIC2 served as a promotive regulator in GC, aggravating growth and stemness in GC progression through the Wnt/β-catenin pathway. This discovery hinted that ZIC2 may be a valid target for anticancer treatment.

Keywords: GC; Stemness; Wnt/β-catenin pathway; ZIC2.