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

Autor:	Bagheri M; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA., Aisha Mohamed G; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA., Mohamed Saleem MA; Lifebytes India Pvt Ltd, Bengaluru, India., Ognjenovic NB; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA., Lu H; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA., Kolling FW; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA., Wilkins OM; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA.; Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover NH 03755 USA., Das S; Lifebytes India Pvt Ltd, Bengaluru, India., La Croix IS; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA., Nagaraj SH; Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.; Translational Research Institute, Brisbane QLD 4102, Australia., Muller KE; Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA., Gerber SA; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA., Miller TW; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA., Pattabiraman DR; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.; Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03756, USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 21. Date of Electronic Publication: 2023 Apr 21.
DOI:	10.1101/2023.04.19.537586
Abstrakt:	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. Competing Interests: Declaration of Conflicts of Interest This study was supported in part by a Sponsored Research Agreement with Eisai Inc.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu