Publication details

Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer

Authors

ABAD Etna GARCIA-MAYEA Yoelsis MIR Cristina SEBASTIAN David ZORZANO Antonio POTĚŠIL David ZDRÁHAL Zbyněk LYAKHOVICH Alex LLEONART Matilde

Year of publication 2019
Type Article in Periodical
Magazine / Source Molecular and Cellurar Proteomic
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.mcponline.org/content/18/2/231
Doi http://dx.doi.org/10.1074/mcp.RA118.001102
Keywords STEM-CELLS; DYSFUNCTION; AUTOPHAGY; HYDROXYCHLOROQUINE; TOXICITY; TARGET; GROWTH; ACID
Description Cancer cells are known to reprogram their metabolism to adapt to adverse conditions dictated by tumor growth and microenvironment. A subtype of cancer cells with stem-like properties, known as cancer stem cells (CSC), is thought to be responsible for tumor recurrence. In this study, we demonstrated that CSC and chemoresistant cells derived from triple negative breast cancer cells display an enrichment of up-and downregulated proteins from metabolic pathways that suggests their dependence on mitochondria for survival. Here, we selected antibiotics, in particular - linezolid, inhibiting translation of mitoribosomes and inducing mitochondrial dysfunction. We provided the first in vivo evidence demonstrating that linezolid suppressed tumor growth rate, accompanied by increased autophagy. In addition, our results revealed that bactericidal antibiotics used in combination with autophagy blocker decrease tumor growth. This study puts mitochondria in a spotlight for cancer therapy and places antibiotics as effective agents for eliminating CSC and resistant cells.
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