title: Targeting lactate transport suppresses in vivo breast tumour growth.
abstract: BACKGROUND
  Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment.
  
  
  RESULTS
  The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth.
  
  
  CONCLUSIONS
  This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Morais-Santos
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Miranda-Gonçalves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: António H J
authors.initials: AH
authors.lastname: Moreira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sandro
authors.initials: S
authors.lastname: Queirós
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.|DIGARC - Technology School, Polytechnic Institute of Cávado and Ave, Barcelos, Portugal.
authors.forename: João L
authors.initials: JL
authors.lastname: Vilaça
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of University of Porto, Porto, Portugal.|Medical Faculty of the University of Porto, Porto, Portugal.|Department of Pathology and Medicine, Laboratoire National de Sante, Dudelange, Luxembourg.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.|Laboratory of Medical Investigation (LIM-14), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of University of Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Paredes
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.|Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, Sao Paulo, Brazil.
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human
keywords: Warburg effect; breast carcinoma; hypoxia; lactate; monocarboxylate transporters