Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
By J. Chiche, M. Brahimi-Horn, J. Pouysségur. Journal of Cellular and Molecular Medicine, 2009
642 citations recorded by the source corpus.
• Introduction • Intracellular pH regulation controls energy balance and cell proliferation: chemical and biological proof of principle ‐ Chemical proof of principle ‐ Biological proof of principle: the role of the Na+/H+ exchanger‐1 • Oncogene activation and transformation cause acidosis ‐ Warburg effect (aerobic glycolysis) ‐ Inhibition of tumour suppressor genes and oncogene activation drive the ‘Warburg effect’ and cause acidosis ‐ Neoplastic transformation drives intracellular alkalinization and extracellular acidification through the activation and up‐regulation of pHi‐regulating systems • Hypoxia promotes acidosis by shifting from oxidative phosphorylation to glycolytic metabolism ‐ HIF mediates cellular adaptation to low oxygen availability ‐ HIF‐induced metabolic reprogramming in response to tumour hypoxia causes acidosis ‐ Acidosis may affect HIF‐α stabilization and on HIF‐induced gene regulation • Hypoxia enhances the expression and activity of pHi‐regulating systems to promote cell survival and invasion ‐ Hypoxia increases NHE‐1 expression and activity ‐ The hypoxia‐induced membrane‐associated carbonic anhydrases are key enzymes involved in pH homeostasis, cell survival and migration in a hypoxic/acidic microenvironment ‐ CAIX regulation and expression ‐ CAXII regulation and expression ‐ The activity and functions of CAIX and CAXII ‐ The hypoxia‐induced monocarboxylate transporter MCT4, the constitutively expressed MCT1 and their chaperone CD147 are key plasma‐membrane proteins involved in pH regulation, energy balance, tumour progression and metastasis ‐ MCT regulation, expression, structure and implication of their chaperone CD147 ‐ The MCT1, MCT4 and CD147 activity and functions • Strategies taking advantage of changes in the oxygen level, energy balance and pH homeostasis to target primary tumours and metastases ‐ Decreasing the pHi of hypoxic cells of the primary tumour by inhibiting key pHi‐regulating systems to collapse ATP production ‐ Increasing pHo and the extracellular buffering capacity in targeting metastasis and reducing multidrug resistance • Conclusion
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/9f720872f06c47d483489a9df2d2ab59a6ddc669
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Citations in the corpus
- HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, neutral): “SLC9A1 encodes sodium-hydrogen exchanger 1 (NHE1), which actively pumps H + ions into the extracellular space (50).”
- Targeting hypoxia in cancer therapy (2011, background): “Disruption of pH homeostasis by targeting MCTs (such as MCT1 and MCT4) and carbonic anhydrases in hypoxic tumour cells has been proposed as a tumour-selective approac”
- The Acidic Tumor Microenvironment as a Driver of Cancer. (2019, background): “It is generally reported that acidic and hypoxic regions overlap (17).”
- Flavonoids as Anticancer Agents (2020, background): “The main metabolic alterations of the tumor cells involve increased aerobic glycolysis [42], deregulated pH [43], impaired lipid metabolism [44], increased generation of ROS [45], and compromised enzyme activities [38,46] (Figure 8).”