Faculty Collaboration Database

Pharmacological Induction of mesenchymal-epithelial transition chemosensitizes breast cancer cells and prevents metastatic progression. bioRxiv 2023 Apr 21

Date

05/03/2023

Pubmed ID

37131809

Pubmed Central ID

PMC10153261

DOI

10.1101/2023.04.19.537586

Abstract

The epithelial-mesenchymal transition (EMT) is a developmental program co-opted by tumor cells that aids the initiation of the metastatic cascade. Tumor cells that undergo EMT are relatively chemoresistant, and there are currently no therapeutic avenues specifically targeting cells that have acquired mesenchymal traits. We show that treatment of mesenchymal-like triple-negative breast cancer (TNBC) cells with the microtubule-destabilizing chemotherapeutic eribulin, which is FDA-approved for the treatment of advanced breast cancer, leads to a mesenchymal-epithelial transition (MET). This MET is accompanied by loss of metastatic propensity and sensitization to subsequent treatment with other FDA-approved chemotherapeutics. We uncover a novel epigenetic mechanism of action that supports eribulin pretreatment as a path to MET induction that curtails metastatic progression and the evolution of therapy resistance.

Author List

Bagheri M, Aisha Mohamed G, Mohamed Saleem MA, Ognjenovic NB, Lu H, Kolling FW, Wilkins OM, Das S, La Croix IS, Nagaraj SH, Muller KE, Gerber SA, Miller TW, Pattabiraman DR

Author

Todd W. Miller PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin