A novel therapeutic strategy targeting the mesenchymal phenotype of malignant pleural mesothelioma by suppressing LSD1 [array]

Transcriptome analysis following knock down of LSD1 in ACC-MESO-1 cells. Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a low overall survival; however, no significant treatment advances have been made in the past 15 years. In this study we investigated whether targeting lysine-specific demethylase 1 (LSD1/KDM1), a histone-modifying enzyme responsible for demethylating histone H3 lysine 4 and lysine 9, could represent a novel therapeutic strategy for patients with MPM. We found that suppressing LSD1 induces an epithelial phenotype in sarcomatoid MPM cells, while attenuating the mesenchymal phenotype sensitized MPM cells to cisplatin-induced apoptosis through the FAK pathway. To investigate the potential mechanisms underlying FAK pathway activation, we performed transcriptome analysis using two different shRNA constructs against the LSD1. We performed transcriptome analysis in ACC-MESO-1 cells infected with shLSD1 or control using the Clariom S Array platform.