Aberrant Expression of Plastin-3 Via Copy Number Gain Induces the Epithelial-Mesenchymal Transition in Circulating Colorectal Cancer Cells

Plastin-3 (PLS3) is a novel marker for circulating tumor cells (CTCs) in colorectal cancer (CRC). We sought to investigate the mechanisms mediating the aberrant expression of PLS3, the role of PLS3 in the epithelial-mesenchymal transition (EMT), and its association with the acquisition of invasive and metastatic abilities in human CRC. The expression levels of PLS3 messenger RNA in the tumor drainage venous blood (TDB) were examined in 177 CRC cases, and the associations between PLS3 expression and Xq23 copy numbers were analyzed in 132 CRC samples. We then established a stable PLS3-expressing CRC cell line and assessed the role of PLS3 in the EMT. In clinical CRC cases, high expression of PLS3 in CTCs of TDB as well as peripheral blood was established as an independent prognostic factor of overall survival (p < 0.001), and the copy number gain of Xq23, which is the locus of the PLS3 gene, was significantly related to PLS3 overexpression. PLS3 induced the EMT via transforming growth factor (TGF)-beta signaling and resulted in the acquisition of invasive ability in CRC cells. The aberrant expression of PLS3 was associated with copy number gain in CTCs from primary tumors and was involved in the regulation of the EMT, contributing to a poor prognosis in CRC patients.