ArticleOncogene2016
Disrupting Na⁺, HCO₃⁻-cotransporter NBCn1 (Slc4a7) delays murine breast cancer development.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- Pooled it
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread.Science advances · 2026Article
- SLC4A7 Drives NSCLC Progression and Immune Evasion via pH Dysregulation: Its Targeting Synergizes with Anti-PD-1/L1 Therapy.International journal of biological sciences · 2026Article
- The Role of Tumor pH in Breast Cancer Imaging: Biology, Diagnostic Applications, and Emerging Techniques.Diagnostics (Basel, Switzerland) · 2025Review
- Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.The Journal of clinical investigation · 2025Article
- CryoEM and computational modeling structural insights into the pH regulator NBCn1.Nature communications · 2025Article
- Loss of NaActa physiologica (Oxford, England) · 2025Article
- Acid affairs in anti-tumour immunity.Cancer cell international · 2024Review
- Mimicking and analyzing the tumor microenvironment.Cell reports methods · 2024Review
- Review
- Acid-base transporters in the context of tumor heterogeneity.Pflugers Archiv : European journal of physiology · 2024Review
- Antibodies toward NaBritish journal of cancer · 2024Article
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- Cancer cell invasion alters the protein profile of extracellular vesicles.Journal of extracellular biology · 2023Article
- Trafficking of carbonic anhydrase 12 and bicarbonate transporters by histamine stimulation mediates intracellular acidic scenario in lung cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer.Breast cancer research : BCR · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased metabolism and insufficient blood supply cause acidic waste product accumulation in solid cancers. During carcinogenesis, cellular acid extrusion is upregulated but the underlying molecular mechanisms and their consequences for cancer growth and progression have not been established. Genome-wide association studies have indicated a possible link between the Na⁺, HCO₃⁻-cotransporter NBCn1 (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1 knockout (KO) for breast cancer development. NBCn1 protein expression increased 2.5-fold during breast carcinogenesis and was responsible for the increased net acid extrusion and alkaline intracellular pH of breast cancer compared with normal breast tissue. Genetic disruption of NBCn1 delayed breast cancer development: tumor latency was ~50% increased while tumor growth rate was ~65% reduced in NBCn1 KO compared with wild-type (WT) mice. Breast cancer histopathology in NBCn1 KO mice differed from that in WT mice and included less aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice contained higher concentrations of glucose and lower concentrations of lactate than that in WT mice. Independently of NBCn1 genotype, the cleaved fraction of poly(ADP-ribose) polymerase (PARP)-1 and expression of monocarboxylate transporter (MCT)1 increased while phosphorylation of Akt and ERK1 decreased as functions of tumor volume. Cell proliferation, evaluated from Ki-67 and phospho-histone H₃staining, was ~60% lower in breast cancer of NBCn1 KO than that of WT mice when corrected for variations in tumor size. We conclude that NBCn1 facilitates acid extrusion from breast cancer tissue, maintains the alkaline intracellular environment and promotes aggressive cancer development and growth.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.