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Transport Metabolons and Acid/Base Balance in Tumor Cells

期刊

CANCERS
卷 12, 期 4, 页码 -

出版社

MDPI
DOI: 10.3390/cancers12040899

关键词

carbonic anhydrase; proton antenna; tumor metabolism; tumor cell migration

类别

资金

  1. Deutsche Forschungsgemeinschaft [BE 4310/6-1, De 231/24]
  2. International Research Training Group [IRTG 1830/1]
  3. Stiftung Rheinland-Pfalz fur Innovation [961-386261/957]
  4. Landesschwerpunkt Membrantransport
  5. Research Initiative BioComp

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Solid tumors are metabolically highly active tissues, which produce large amounts of acid. The acid/base balance in tumor cells is regulated by the concerted interplay between a variety of membrane transporters and carbonic anhydrases (CAs), which cooperate to produce an alkaline intracellular, and an acidic extracellular, environment, in which cancer cells can outcompete their adjacent host cells. Many acid/base transporters form a structural and functional complex with CAs, coined transport metabolon. Transport metabolons with bicarbonate transporters require the binding of CA to the transporter and CA enzymatic activity. In cancer cells, these bicarbonate transport metabolons have been attributed a role in pH regulation and cell migration. Another type of transport metabolon is formed between CAs and monocarboxylate transporters, which mediate proton-coupled lactate transport across the cell membrane. In this complex, CAs function as proton antenna for the transporter, which mediate the rapid exchange of protons between the transporter and the surroundings. These transport metabolons do not require CA catalytic activity, and support the rapid efflux of lactate and protons from hypoxic cancer cells to allow sustained glycolytic activity and cell proliferation. Due to their prominent role in tumor acid/base regulation and metabolism, transport metabolons might be promising drug targets for new approaches in cancer therapy.

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