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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00107512" target="_blank" >RIV/00216224:14740/19:00107512 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mcponline.org/content/18/2/231" target="_blank" >https://www.mcponline.org/content/18/2/231</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/mcp.RA118.001102" target="_blank" >10.1074/mcp.RA118.001102</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and Cellurar Proteomic

ISSN

1535-9476

e-ISSN

1535-9484

Svazek periodika

18

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

231-244

Kód UT WoS článku

000457454000005

EID výsledku v databázi Scopus

2-s2.0-85060924298