Article Abstract

From “high” ZEB1 to “low” B-cell lymphoma 2-interacting mediator of cell death (BIM)—an epithelial-mesenchymal transition (EMT)-associated drug resistance pathway elucidated

Authors: Fabrizio Marcucci, Cristiano Rumio

Abstract

A recently published article (1) shows that ZEB1, one of the pivotal transcription factors involved in the induction of epithelial-mesenchymal transition (EMT) in tumor cells, inhibits the expression of the proapoptotic factor B-cell lymphoma (BCL) 2-interacting mediator of cell death (BIM) by binding directly to the BIM promoter and repressing its transcription. This mediates the resistance of epidermal growth factor receptor (EGFR)-mutant lung cancer cells with a mesenchymal phenotype towards EGFR inhibitor (EGFRi)- induced apoptosis. These results are of considerable interest both in terms of our knowledge about the fundamental mechanisms governing EMT-associated effects, as well as their potential therapeutic implications. In order to put the findings in a broader context we will briefly summarize our current knowledge about EMT and its effects.