A novel EMT-selective small molecule induces ER stress

Carcinoma cells can acquire key malignant traits by reprogramming their differentiation state via an epithelial-to-mesenchymal transition (EMT). Cancer cells that undergo EMT become invasive and resist a wide range of therapies including most chemotherapy drugs and radiation. Such cells are also able to efficiently seed primary and metastatic tumors, making them functionally indistinguishable from tumor-initiating or cancer stem-like cells (TICs or CSCs). Therefore, there is significant interest in finding vulnerabilities of cancer cells that have undergone EMT. A potent EMT-selective small molecule was discovered through a large-scale chemical screen. We used microarray analysis to understand the biological effects of this compound. HMLE_ctrl (human MECs, infected with a pBabe-shGFP retrovirus) and HMLE_Twist (human MECs, infected with a pBabe-Twist retrovirus) cells were treated with solvent control (DMSO), 5 µM or 10 µM of Cmp302 for 6 hours. Microarray analysis was performed to profile global gene expression.