ArticleOncotarget2015
The Na⁺/H⁺ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- NHE1-Mediated Metabolic Reprogramming in Cancer.Metabolites · 2026Review
- Voltage-Gated sodium channel Nav1.6 mediates glioblastoma proliferation and migration via NaMolecular biology reports · 2025Article
- Review
- Acid-base transporters in the context of tumor heterogeneity.Pflugers Archiv : European journal of physiology · 2024Review
- Exploring monocarboxylate transporter inhibition for cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- Crosstalk between tumor acidosis, p53 and extracellular matrix regulates pancreatic cancer aggressiveness.International journal of cancer · 2023Article
- Targeting Na-H exchanger 1 overcomes nuclear factor kappa B-mediated tumor resistance to radiotherapy.Neoplasia (New York, N.Y.) · 2023Article
- Review
- Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms.Cancers · 2022Review
- Permissive role of NaMolecular and cellular biochemistry · 2022Article
- Role of pH Regulatory Proteins and Dysregulation of pH in Prostate Cancer.Reviews of physiology, biochemistry and pharmacology · 2022Article
- The complex relationship between multiple drug resistance and the tumor pH gradient: a review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Ion Transporting Proteins and Cancer: Progress and Perspectives.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Therapeutic efficacy of proton transport inhibitors alone or in combination with cisplatin in triple negative and hormone sensitive breast cancer models.Cancer medicine · 2022Article
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Roles of the NaInternational journal of molecular sciences · 2021Article
- Tracing of intracellular pH in cancer cells in response to Taxol treatment.Cell cycle (Georgetown, Tex.) · 2021Article
- Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of Na⁺/H⁺ exchanger isoform one (NHE1) activity is a hallmark of cells undergoing tumorigenesis and metastasis, the leading cause of patient mortality. The acidic tumor microenvironment is thought to facilitate the development of resistance to chemotherapy drugs and to promote extracellular matrix remodeling leading to metastasis. Here, we investigated NHE1 as a co-adjuvant target in paclitaxel chemotherapy of metastatic breast cancer. We generated a stable NHE1-knockout of the highly invasive, triple-negative, MDA-MB-231 breast cancer cells. The NHE1-knockout cells proliferated comparably to parental cells, but had markedly lower rates of migration and invasion in vitro. In vivo xenograft tumor growth in athymic nude mice was also dramatically decreased compared to parental MDA-MB-231 cells. Loss of NHE1 expression also increased the susceptibility of knockout cells to paclitaxel-mediated cell death. NHE1 inhibition, in combination with paclitaxel, resulted in a dramatic decrease in viability, and migratory and invasive potential of triple-negative breast cancer cells, but not in hormone receptor-positive, luminal MCF7 cells. Our data suggest that NHE1 is critical in triple-negative breast cancer metastasis, and its chemical inhibition boosts the efficacy of paclitaxel in vitro, highlighting NHE1 as a novel, potential co-adjuvant target in breast cancer chemotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.