2. Academic Validation
  3. Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer

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

  • Mol Cell Proteomics. 2019 Feb;18(2):231-244. doi: 10.1074/mcp.RA118.001102.
Etna Abad 1,  Yoelsis García-Mayea 1,  Cristina Mir 1,  David Sebastian 2,  Antonio Zorzano 2,  David Potesil 3,  Zbynek Zdrahal 4,  Alex Lyakhovich 5,  Matilde E Lleonart 6
Affiliations

Affiliations

  • 1 Biomedical Research in Cancer Stem Cell Group, Pathology Department, Vall d'Hebron Hospital, 08035, Passeig Vall d'Hebron 119-129, 08035 Barcelona. Barcelona, Spain.
  • 2 Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain 08028;; Departament de Bioquímica i Biomedicina Molecular, Universitat de Barcelona, c/ Baldiri Reixac, 10-12, Barcelona 08028, Spain;; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain.
  • 3 CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
  • 4 CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic;; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
  • 5 Biomedical Research in Cancer Stem Cell Group, Pathology Department, Vall d'Hebron Hospital, 08035, Passeig Vall d'Hebron 119-129, 08035 Barcelona. Barcelona, Spain;. Electronic address: alex.lyakhovich@vhir.org.
  • 6 Biomedical Research in Cancer Stem Cell Group, Pathology Department, Vall d'Hebron Hospital, 08035, Passeig Vall d'Hebron 119-129, 08035 Barcelona. Barcelona, Spain;; Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Barcelona, Spain. Electronic address: matilde.lleonart@vhir.org.
PMID: 30373788 DOI: 10.1074/mcp.RA118.001102
Abstract

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.

Keywords

Antibiotics; Autophagy; Breast Cancer; Cancer Biology; Cancer Stem Cells; Chemoresistance; Clinical Proteomics; Mitochondria; Mitochondria Function or Biology; NMR; NMR-metabolomic; Stem Cells.

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