Abstract
Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCC.
Highlights
Otto Warburg first reported on the metabolic phenomenon of many tumor cells, namely, their high anaerobic glycolytic activity, even in the presence of sufficient oxygen [1]
The aim of the present review is to provide the reader with a platform for studying the potential of proton exchangers as diagnostic and therapeutic tools in oral squamous cell carcinoma (OSCC)
Despite the fact that more than 50 genes may be induced by hypoxia via hypoxia-inducible factor 1α (HIF-1α), genes of the CAIX
Summary
Otto Warburg first reported on the metabolic phenomenon of many tumor cells, namely, their high anaerobic glycolytic activity, even in the presence of sufficient oxygen [1]. This metabolic pathway appears in contrast to the highly efficient oxidative phosphorylation used by most eukaryotes in order to yield the energy to sustain homeostasis [2]. These changes, both intracellularly and in the extracellular matrix (ECM), are related to cancer progression and metastasis due to their ability to create acid–base disturbances, inducing hypoxia [3].
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