The zinc transporter LIV-1 is a novel regulator of stemness in pancreatic cancer cells

Abstract

Objective. Recent studies have identified the existence a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue. Cancer stem cells harbor highly tumorigenic and chemo-resistant phenotypes, which lead to recurrence or re-growth of the tumor after surgery. The mechanisms that regulate the stemness of cancer cells remain largely unknown. We hypothesized that LIV-1, a zinc transporter, regulates the stemness in pancreatic cancer cells. Material and methods. We established two stable Panc-1 pancreatic cancer cell lines in which LIV-1 expression was knocked down by the introduction of siRNA against LIV-1. Expression of cancer stem cell–related molecules was examined by quantitative real-time PCR. Expression of ATP-binding cassette sub-family G member 2 was also determined by flow cytometry. Spheroid culture was performed in low-adhesion coated plates. Cell migration was determined by using a modified 2-chamber migration assay. In vivo tumor formation was assessed in nude mice after the subcutaneous injection of cancer cells. The Agilent's miRNA microarray was used to identify differentially expressed miRNAs. Results. Knockdown of LIV-1 expression resulted in (i) decreased expression of cancer stem cell-related molecules such as LIN28 and ATP-binding cassette sub-family G member 2, (ii) decreased spheroid-forming ability, (iii) decreased migration, (iv) decreased incidence of tumor formation in nude mice, and (v) upregulation of miR-7 expression. Conclusions. Our results suggest that LIV-1 might act as a novel regulator of stemness in pancreatic cancer cells.