ArticleNature communications2017
Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 66 citations in OpenAlex.
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Hyperbaric Oxygen Regulates Tumor pH to Boost Copper-Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells.Exploration (Beijing, China) · 2025Article
- TMEM184B modulates endolysosomal acidification via the vesicular proton pump.Journal of cell science · 2025Article
- Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy.Theranostics · 2025Review
- PFKFB2 is a favorable prognostic biomarker for colorectal cancer by suppressing metastasis and tumor glycolysis.Journal of cancer research and clinical oncology · 2023Article
- Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles.Pharmaceutics · 2023Review
- Altered distribution and localization of organellar NaTranslational psychiatry · 2023Article
- Hypoxia promotes EV secretion by impairing lysosomal homeostasis in HNSCC through negative regulation of ATP6V1A by HIF-1α.Journal of extracellular vesicles · 2023Article
- Co-delivery of carbonic anhydrase IX inhibitor and doxorubicin as a promising approach to address hypoxia-induced chemoresistance.Drug delivery · 2022Article
- Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.Oncogene · 2022Article
- Article
- Targeting the Ezrin Adaptor Protein Sensitizes Metastatic Breast Cancer Cells to Chemotherapy and Reduces Neoadjuvant Therapy-induced Metastasis.Cancer research communications · 2022Article
- Facile synthesis of near-infrared responsive on-demand oxygen releasing nanoplatform for precise MRI-guided theranostics of hypoxia-induced tumor chemoresistance and metastasis in triple negative breast cancer.Journal of nanobiotechnology · 2022Article
- Article
- Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles.American journal of cancer research · 2022Article
- Establishment of a ccRCC patient-derived chick chorioallantoic membrane model for drug testing.Frontiers in medicine · 2022Article
- NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load.eLife · 2021Article
- Article
- SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification. The acidity of the vesicular lumen, together with the alkaline pH of the cytoplasm, gives rise to a strong intracellular pH gradient that drives intravesicular drug trapping and chemoresistance. Endosome hyperacidification is due to the relocalization of the Na
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