ArticleMolecular oncology2018
Mammary epithelium-specific inactivation of V-ATPase reduces stiffness of extracellular matrix and enhances metastasis of breast cancer.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- The Potential Role of Tumor Microorganisms in Remodeling Tumor Biomechanical Signals and Application Strategies in Tumor Therapy.Microorganisms · 2026Review
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- Cancer-Associated Fibroblasts in the Treatment of Intrahepatic Cholangiocarcinoma: Present and Prospects.Journal of hepatocellular carcinoma · 2026Review
- Premetastatic niche mechanics and organotropism in breast cancer.npj biological physics and mechanics · 2025Review
- Epirubicin induces cardiotoxicity through disrupting ATP6V0A2-dependent lysosomal acidification and triggering ferroptosis in cardiomyocytes.Cell death discovery · 2024Article
- Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.Proteome science · 2023Article
- Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement.Clinical and experimental dental research · 2023Article
- Extracellular matrix remodelling and stiffening contributes to tumorigenesis of salivary carcinoma ex pleomorphic adenoma--A study based on patient-derived organoids.Cell & bioscience · 2023Article
- Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway.Acta biochimica et biophysica Sinica · 2022Article
- The a subunit isoforms of vacuolar-type proton ATPase exhibit differential distribution in mouse perigastrulation embryos.Scientific reports · 2022Article
- The New Face of a Well-Known Antibiotic: A Review of the Anticancer Activity of Enoxacin and Its Derivatives.Cancers · 2022Review
- Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis.Cancer communications (London, England) · 2022Review
- Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy.Journal of hematology & oncology · 2022Review
- How Reciprocal Interactions Between the Tumor Microenvironment and Ion Transport Proteins Drive Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Angiogenesis-Related Immune Signatures Correlate With Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity in Hepatocellular Carcinoma.Frontiers in molecular biosciences · 2021Article
- Article
- Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1) Are Associated with Progression and Prognosis of Esophageal Cancer as Identified by Integrated Expression Profiles Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Cancer-associated V-ATPase induces delayed apoptosis of protumorigenic neutrophils.Molecular oncology · 2020Article
- Dissecting the heterogeneity of the alternative polyadenylation profiles in triple-negative breast cancers.Theranostics · 2020Observational
- V-ATPase in cancer progression: Two sides of the same coin.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular matrix (ECM) critically impacts tumor progression and is influenced by both cancer and host tissue cells. While our understanding of cancer cell ECM remodeling is widespread, the importance of host tissue ECM, which provides initial congenial environment for primary tumor formation, is partly understood. Here, we report a novel role of epithelial cell-associated vacuolar ATPase 'a2' isoform (a2V) in regulating breast tissue ECM stiffness to control metastasis. Using a mammary gland-specific a2V-knockout model, we show that in the absence of a2V, breast tumors exhibit atypically soft tumor phenotype, less tumor rigidity, and necrotic tumor microenvironment. These tumors contain a decreased number of cancer cells at primary tumor site, but showed extensive metastases compared to control. Nanomechanical evaluation of normal breast tissues revealed a decrease in stiffness and collagen content in ECM of a2V-deleted breast tissues. Mechanistically, inhibition of a2V expression caused dispersed Golgi morphology with relocation of glycosyltransferase enzymes to early endosomes in mammary epithelial cells. This resulted in defective glycosylation of ECM proteins and production of compromised ECM that further influenced tumor metastasis. Clinically, in patients with cancer, low a2V expression levels in normal breast tissue correlated with lymph node metastasis. Thus, using a new knockout mouse model, we have identified a2V expression in epithelial cells as a key requirement for proper ECM formation in breast tissue and its expression levels can significantly modulate breast tumor dissemination. Evaluation of a2V expression in normal breast tissues can help in identifying patients with high risk of developing metastases.
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