title: Value of pH regulators in the diagnosis, prognosis and treatment of cancer.
abstract: Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets.
authors.affiliation: Life and Health Sciences Research Institute (ICVS)/School of Medicine/University of Minho, Campus de Gualtar, Braga, 4710-057, 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 Medicine/University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Tavares-Valente
authors.affiliation: IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; CBMA - Center of Molecular and Environmental Biology/Department of Biology/University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal.
authors.forename: Odília
authors.initials: O
authors.lastname: Queirós
authors.affiliation: Life and Health Sciences Research Institute (ICVS)/School of Medicine/University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: fbaltazar@ecsaude.uminho.pt.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; D017923:Sodium-Hydrogen Exchangers; D000251:Adenosine Triphosphatases; D002256:Carbonic Anhydrases
keywords: ATPases; Carbonic anhydrases; Monocarboxylate transporters; Sodium-hydrogen exchangers; pH regulators