Common metabolic pathways implicated in resistance to chemotherapy point to a key mitochondrial role in breast cancer (original) (raw)

2018, Molecular & cellular proteomics : MCP

Cancer cells are known to reprogram their metabolism to adapt to adverse conditions dictated by tumour growth and microenvironment. A subtype of cancer cells with stem-like properties, known as cancer stem cells (CSC), is thought to be responsible for tumour recurrence. In this study, we demonstrated that CSC and chemoresistant cells derived from triple negative breast cancer cells display an enrichment of up- and down-regulated 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 tumour growth rate, accompanied by increased autophagy. In addition, our results revealed that bactericidal antibiotics used in combination with autophagy blocker decrease tumour growth. This study puts mitochondria in a spotlight for cancer therapy and...