Proton-sensing G protein-coupled receptors as regulators of cell proliferation and migration during tumor growth and wound healing.
Dysregulation of pH is a feature of both tumor growth and tissue repair. In tumors, microenvironmental changes, like in lactate metabolism, lead to altered intra- and extracellular pH (pHi, pHe) and vice versa. In wounds, barrier disruption results in extensive variations in pHeon the wound surface. It is known that altered extracellular proton concentrations have a major impact on cell turnover and migration as well as on the metabolic activity of cells involved in tumor spread and wound closure. The proton-sensing G protein-coupled receptors (GPCRs) GPR4, GPR65 (TDAG8), GPR68 (OGR1) and GPR132 (G2A) are activated via a decrease in pHeand transduce this signal to molecular intracellular pathways. Based on the current knowledge, we speculate on the role of proton-sensing GPCRs in wound healing and on their potential as mechanistic linkers of tumor growth and tissue repair.
Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
Katharina T
KT
Weiß
Department of Internal Medicine III, Oncology, University Medical Center Regensburg, Regensburg, Germany.
Matthias
M
Fante
Department of Surgery, University Medical Center Regensburg, Regensburg, Germany.
Gudrun
G
Köhl
Institute of Human Genetics, University of Cologne, Cologne, Germany.
Julia
J
Schreml
Department of Otorhinolaryngology, University Medical Center Regensburg, Regensburg, Germany.
Frank
F
Haubner
Department of Internal Medicine III, Oncology, University Medical Center Regensburg, Regensburg, Germany.
Marina
M
Kreutz
Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
Sonja
S
Haverkampf
Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
Mark
M
Berneburg
Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
Stephan
S
Schreml
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D059016:Tumor Microenvironment; D014945:Wound Healing / Q000502:physiology*
D018797:Cell Cycle Proteins; C115270:G2A receptor; C091670:GPR4 protein, human; C517811:GPR4 protein, mouse; C513334:GPR65 protein, human; C513337:GPR65 protein, mouse; C486281:GPR68 protein, human; C525539:GPR68 protein, mouse; D043562:Receptors, G-Protein-Coupled
proton signalling; tissue repair; tumor metabolism; wounds