Zinc transporter SLC39A7/ZIP7 contributes to the tumorigenic potentials of human colorectal cancer cells

Abstract

Intestinal epithelium undergoes a continuous self-renewing process to maintain the intestinal homeostasis. We recently demonstrated the essential role of zinc transporter ZIP7 in maintenance of the self-renewing process of intestinal epithelium by resolving endoplasmic reticulum (ER) stress in intestinal stem cells and its daughter cells. Alternatively, this suggests that ZIP7 would be important for adaptation to ER stress. It is conceivable that there could be common mechanisms between self-renewing process and tumorigenesis. The study was conducted to investigate the role of zinc transporter ZIP7 in colorectal cancer by depleting ZIP7 using RNA interference by siRNA or shRNA transduction. Deletion of ZIP7 in several human colorectal cancer cell lines (HT29, SW480, and HCT116) induced a pronounced loss of clonogenicity and blocked cell proliferation assessed by cell counting assay or crystal violet analysis, an effect which was associated with increased apoptotic cell death as indicated by flow-cytometry analysis. Colorectal cancer cells, which are deficient in ZIP7 had lower cancer stem cell potential by the anchorage-independent cancer stem cell model assay. Moreover, xenograft assays in immunodeficient mice showed that tumors generated by ZIP7-depleted cells were smaller than those generated by control cells, showing the requirement of ZIP7 expression in cancer cells for tumorigenicity in vivo. These findings suggest that ZIP7 contributes to the tumorigenic potential of colorectal cancer and ZIP7 may represent an attractive target in suppressing proliferation of colorectal cancer cells.