The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis
Abstract
Recent research has highlighted the fundamental role of the tumour's extracellular metabolic microenvironment in malignant invasion. This microenvironment is acidified primarily by the tumour-cell Na(+)/H(+) exchanger NHE1 and the H(+)/lactate cotransporter, which are activated in cancer cells. NHE1 also regulates formation of invadopodia - cell structures that mediate tumour cell migration and invasion. How do these alterations of the metabolic microenvironment and cell invasiveness contribute to tumour formation and progression?
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A lower pH value accelerates cell-matrix recombination and lamellipodia formation, further facilitating cell migration.
“Meanwhile, the lower pH value accelerates the cell-matrix recombination and lamellipodia formation, further facilitating cell migration. [40]”
From Multiplex Cellular Microenvironment Detection Based on Surface-Enhanced Raman Scattering Patch (2025) · cites this paper as [40]
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- Authors
- Cardone, R. A., Casavola, V., & Reshkin, S. J.
- Affiliations
- University of Bari Aldo Moro (IT)
- Corresponding author
- Reshkin, Stephan J.
- Venue
- Nature Reviews Cancer
- Published
- 2005-09-20
- Volume
- 5
- Issue
- 10
- Pages
- 786-795
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2060315853
- Cited by
- 897
- References
- 77
- Citations by year
- 2026: 25 · 2025: 23 · 2024: 38 · 2023: 44 · 2022: 33 · 2021: 48 · 2020: 67 · 2019: 44 · 2018: 43 · 2017: 71 · 2016: 62 · 2015: 46 · 2014: 58 · 2013: 63 · 2012: 52
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Consiglio Nazionale delle Ricerche
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- tumour metastasis, extracellular pH, invadopodia, tumor invasion, tumor cell migration, tumor microenvironment, tumor progression
- MeSH terms
- Sodium-Hydrogen Exchanger 1, Animals, Humans, Hydrogen-Ion Concentration, Membrane Proteins, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Signal Transduction, Sodium-Hydrogen Exchangers, Cation Transport Proteins, Mice
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