Abstract
Expression of a mesenchymal phenotype is often associated with invasive/metastatic behaviors of carcinoma cells. Acquisition of a mesenchymal phenotype by a carcinoma cell is known as epithelial-mesenchymal transition (EMT). The membrane-anchored matrix metalloproteinase-regulator RECK is abundant in normal mesenchymal cells. In aggressive carcinomas, however, RECK expression is often downregulated. This apparent paradox prompted us to clarify the relationship between EMT and RECK. We found that TGFβ-induced E-cadherin downregulation, a hallmark of EMT, is accompanied by RECK-upregulation in a non-tumorigenic epithelial cell line (MCF10A). In contrast, the loss of E-cadherin expression is uncoupled from RECK-upregulation in carcinoma-derived cell lines (MCF7, MDA-MB-231, and A549). When RECK was artificially expressed in A549 cells, it showed little effect on EMT but elevated the level of integrin α5 and attenuated cell proliferation and migration. These findings implicate RECK in the regulation of proliferation and migration of normal epithelial cells after EMT and suggest how the uncoupling between EMT and RECK-upregulation impacts on the fates and behaviors of carcinoma cells.