Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UNIPROT:Q86TM3 (
cage
)
29,987
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Exploring the role of stromal osmoregulation in cancer and disease using executable modelling. 3006 15
Prostate cancer is the fourth most commonly diagnosed cancer, and although it is often a slow-growing malignancy, it is the second leading cause of
cancer-associated
deaths in men and the first in Europe and North America. In many forms of cancer, when the disease is a solid tumor confined to one organ, it is often readily treated. However, when the cancer becomes an invasive metastatic carcinoma, it is more often fatal. It is therefore of great interest to identify mechanisms that contribute to the invasion of cells to identify possible targets for therapy. During prostate cancer progression, the epithelial cells undergo epithelial-mesenchymal transition that is characterized by morphological changes, a loss of cell-cell adhesion, and invasiveness. Dysregulation of pH has emerged as a hallmark of cancer with a reversed pH gradient and with a constitutively increased intracellular pH that is elevated above the extracellular pH. This phenomenon has been referred to as "a perfect storm" for cancer progression. Acid-extruding ion transporters include the Na
+
/H
+
exchanger NHE1 (
SLC9A1
), the Na
+
HCO
3
-
cotransporter NBCn1 (SLC4A7), anion exchangers, vacuolar-type adenosine triphosphatases, and the lactate-H
+
cotransporters of the monocarboxylate family (MCT1 and MCT4 (SLC16A1 and 3)). Additionally, carbonic anhydrases contribute to acid transport. Of these, several have been shown to be upregulated in different human cancers including the NBCn1, MCTs, and NHE1. Here the role and contribution of acid-extruding transporters in prostate cancer growth and metastasis were examined. These proteins make significant contributions to prostate cancer progression.
...
PMID:Role of pH Regulatory Proteins and Dysregulation of pH in Prostate Cancer. 3277 52
