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

J 2019

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

ABAD, Etna, Yoelsis GARCIA-MAYEA, Cristina MIR, David SEBASTIAN, Antonio ZORZANO et. al.

Basic information

Original name

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

Authors

ABAD, Etna (724 Spain), Yoelsis GARCIA-MAYEA (724 Spain), Cristina MIR (724 Spain), David SEBASTIAN (724 Spain), Antonio ZORZANO (724 Spain), David POTĚŠIL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Alex LYAKHOVICH (724 Spain) and Matilde LLEONART (724 Spain)

Edition

Molecular and Cellurar Proteomic, American Society for Biochemistry and Molecular Biology, 2019, 1535-9476

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.870

RIV identification code

RIV/00216224:14740/19:00107512

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1074/mcp.RA118.001102

UT WoS

000457454000005

Keywords in English

STEM-CELLS; DYSFUNCTION; AUTOPHAGY; HYDROXYCHLOROQUINE; TOXICITY; TARGET; GROWTH; ACID

Abstract

V originále

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.

Links

GBP206/12/G151, research and development project

Name: Centrum nových přístupů k bioanalýze a molekulární diagnostice

LM2015043, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90043, large research infrastructures

Name: CIISB

Citovat

ABAD, Etna, Yoelsis GARCIA-MAYEA, Cristina MIR, David SEBASTIAN, Antonio ZORZANO, David POTĚŠIL, Zbyněk ZDRÁHAL, Alex LYAKHOVICH and Matilde LLEONART. Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer. Molecular and Cellurar Proteomic. American Society for Biochemistry and Molecular Biology, 2019, vol. 18, No 2, p. 231-244. ISSN 1535-9476. Available from: https://dx.doi.org/10.1074/mcp.RA118.001102.

@article{1545967,
   author = {Abad, Etna and GarciaandMayea, Yoelsis and Mir, Cristina and Sebastian, David and Zorzano, Antonio and Potěšil, David and Zdráhal, Zbyněk and Lyakhovich, Alex and Lleonart, Matilde},
   article_number = {2},
   doi = {http://dx.doi.org/10.1074/mcp.RA118.001102},
   keywords = {STEM-CELLS; DYSFUNCTION; AUTOPHAGY; HYDROXYCHLOROQUINE; TOXICITY; TARGET; GROWTH; ACID},
   language = {eng},
   issn = {1535-9476},
   journal = {Molecular and Cellurar Proteomic},
   title = {Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer},
   url = {https://www.mcponline.org/content/18/2/231},
   volume = {18},
   year = {2019}
}

TY  - JOUR
ID  - 1545967
AU  - Abad, Etna - Garcia-Mayea, Yoelsis - Mir, Cristina - Sebastian, David - Zorzano, Antonio - Potěšil, David - Zdráhal, Zbyněk - Lyakhovich, Alex - Lleonart, Matilde
PY  - 2019
TI  - Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer
JF  - Molecular and Cellurar Proteomic
VL  - 18
IS  - 2
SP  - 231-244
EP  - 231-244
PB  - American Society for Biochemistry and Molecular Biology
SN  - 15359476
KW  - STEM-CELLS
KW  - DYSFUNCTION
KW  - AUTOPHAGY
KW  - HYDROXYCHLOROQUINE
KW  - TOXICITY
KW  - TARGET
KW  - GROWTH
KW  - ACID
UR  - https://www.mcponline.org/content/18/2/231
L2  - https://www.mcponline.org/content/18/2/231
N2  - 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.
ER  -

ABAD, Etna, Yoelsis GARCIA-MAYEA, Cristina MIR, David SEBASTIAN, Antonio ZORZANO, David POTĚŠIL, Zbyněk ZDRÁHAL, Alex LYAKHOVICH and Matilde LLEONART. Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer. \textit{Molecular and Cellurar Proteomic}. American Society for Biochemistry and Molecular Biology, 2019, vol.~18, No~2, p.~231-244. ISSN~1535-9476. Available from: https://dx.doi.org/10.1074/mcp.RA118.001102.

Detailed Information on Publication Record