The acid-base transport proteins NHE1 and NBCn1 regulate cell cycle progression in human breast cancer cells Article Swipe
Mette Flinck
,
Signe Hoejland Kramer
,
Julie Schnipper
,
Anne Poder Andersen
,
Stine F. Pedersen
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.6084/m9.figshare.6505886.v1
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.6084/m9.figshare.6505886.v1
Precise acid-base homeostasis is essential for maintaining normal cell proliferation and growth. Conversely, dysregulated acid-base homeostasis, with increased acid extrusion and marked extracellular acidification, is an enabling feature of solid tumors, yet the mechanisms through which intra- and extracellular pH (pHi, pHe) impact proliferation and growth are incompletely understood. The aim of this study was to determine the impact of pH, and specifically of the Na+/H+ exchanger NHE1 and Na+, HCO3− transporter NBCn1, on cell cycle progression and its regulators in human breast cancer cells. Reduction of pHe to 6.5, a common condition in tumors, significantly delayed cell cycle progression in MCF-7 human breast cancer cells. The NHE1 protein level peaked in S phase and that of NBCn1 in G2/M. Steady state pHi changed through the cell cycle, from 7.1 in early S phase to 6.8 in G2, recovering again in M phase. This pattern, as well as net acid extrusion capacity, was dependent on NHE1 and NBCn1. Accordingly, knockdown of either NHE1 or NBCn1 reduced proliferation, prolonged cell cycle progression in a manner involving S phase prolongation and delayed G2/M transition, and altered the expression pattern and phosphorylation of cell cycle regulatory proteins. Our work demonstrates, for the first time, that both NHE1 and NBCn1 regulate cell cycle progression in breast cancer cells, and we propose that this involves cell cycle phase-specific pHi regulation by the two transporters.
Related Topics
Concepts
Cell cycle progression
Human breast
Breast cancer
Cancer
Base (topology)
Cell cycle
Chemistry
Cell biology
Computational biology
Biology
Cancer research
Cell
Biochemistry
Genetics
Mathematics
Mathematical analysis
Metadata
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- https://doi.org/10.6084/m9.figshare.6505886.v1
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All OpenAlex metadata
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https://openalex.org/W4394536774Canonical identifier for this work in OpenAlex
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https://doi.org/10.6084/m9.figshare.6505886.v1Digital Object Identifier
- Title
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The acid-base transport proteins NHE1 and NBCn1 regulate cell cycle progression in human breast cancer cellsWork title
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datasetOpenAlex work type
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enPrimary language
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2018Year of publication
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2018-01-01Full publication date if available
- Authors
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Mette Flinck, Signe Hoejland Kramer, Julie Schnipper, Anne Poder Andersen, Stine F. PedersenList of authors in order
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https://doi.org/10.6084/m9.figshare.6505886.v1Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.6084/m9.figshare.6505886.v1Direct OA link when available
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Cell cycle progression, Human breast, Breast cancer, Cancer, Base (topology), Cell cycle, Chemistry, Cell biology, Computational biology, Biology, Cancer research, Cell, Biochemistry, Genetics, Mathematics, Mathematical analysisTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.pH<sub>e</sub>) | 41 |
| abstract_inverted_index.phosphorylation | 188 |
| abstract_inverted_index.(pH<sub>i</sub>, | 40 |
| abstract_inverted_index.Na<sup>+</sup>/H<sup>+</sup> | 65 |
| abstract_inverted_index.HCO<sub>3</sub><sup>−</sup> | 70 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 5 |
| citation_normalized_percentile |