Exploring the role of stromal osmoregulation in cancer and disease using executable modelling

David Shorthouse, Angela Riedel, Emma Kerr, Luisa Pedro, Dóra Bihary, Shamith Samarajiwa, Carla P. Martins, Jacqueline Shields*, Benjamin A. Hall

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
3 Downloads (Pure)


Osmotic regulation is a vital homoeostatic process in all cells and tissues. Cells initially respond to osmotic stresses by activating transmembrane transport proteins to move osmotically active ions. Disruption of ion and water transport is frequently observed in cellular transformations such as cancer. We report that genes involved in membrane transport are significantly deregulated in many cancers, and that their expression can distinguish cancer cells from normal cells with a high degree of accuracy. We present an executable model of osmotic regulation and membrane transport in mammalian cells, providing a mechanistic explanation for phenotype change in varied disease states, and accurately predicting behaviour from single cell expression data. We also predict key proteins involved in cellular transformation, SLC4A3 (AE3), and SLC9A1 (NHE1). Furthermore, we predict and verify a synergistic drug combination in vitro, of sodium and chloride channel inhibitors, which target the osmoregulatory network to reduce cancer-associated phenotypes in fibroblasts.

Original languageEnglish
Article number3011
JournalNature Communications
Issue number1
Early online date1 Aug 2018
Publication statusPublished - 1 Dec 2018


  • Osmotic regulation
  • cancer
  • membrane transport


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