Role of P-Glycoprotein Expression and Scaffold Proteins in the Entire Metastasis Process in Lung Cancer Cell Lines

Abstract

Lung cancer metastasis is often associated with poor prognosis for patients. Epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) are important processes in cancer metastasis and are also associated with multidrug resistance (MDR). P-Glycoprotein (P-gp) is one of the efflux transporters responsible for MDR and is anchored to the cell membrane by a family of proteins called ERM (ezrin, radixin, and moesin). The aim of this study was to elucidate the functional changes in P-gp and their mechanisms by continuously inducing EMT and MET in lung cancer cells. EMT was induced by transfecting HCC827 lung cancer cells with the Snail gene, followed by MET induction via dexamethasone. The results suggested that P-gp membrane expression in lung cancer cells increased due to elevated moesin mRNA expression during EMT, followed by increased ezrin expression during MET. The increase in Msn expression did not change during subsequent MET induction, but that in ezrin expression was thought to be further enhanced by the preceding EMT. Furthermore, P-gp membrane expression increased synergistically with the continuous induction of EMT/MET. This study demonstrated that P-gp expression and activity increase at both the EMT and MET stages in cancer metastasis, suggesting that different mechanisms may be involved at each stage.