ArticleLaboratory investigation; a journal of technical methods and pathology2011
The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer.
Article in Laboratory investigation; a journal of technical methods and pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Manzamine A: A promising marine-derived cancer therapeutic for multi-targeted interactions with E2F8, SIX1, AR, GSK-3β, and V-ATPase - A systematic review.European journal of pharmacology · 2025Pooled it
- Niclosamide suppresses breast cancer progression and enhances paclitaxel sensitivity by targeting the ATP6AP1-YY1-XIAP axis.Acta pharmacologica Sinica · 2026Article
- Exploratory Multi-Platform Bioinformatic Analysis of MEAK7 and Its Molecular, Survival, and Immune Associations in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2026Article
- ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.Molecular and cellular biochemistry · 2025Article
- Machine learning integration identifying an eight-gene diagnostic signature for acute mountain sickness.Frontiers in medicine · 2025Article
- The Role of V-ATPase ATP6V0D1 Subunit in Chemoresistance and Ellipticine-Induced Cytoplasmic Vacuolation in Neuroblastoma Cells.Molecular & cellular oncology · 2025Article
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Ion Changes and Signaling under Salt Stress in Wheat and Other Important Crops.Plants (Basel, Switzerland) · 2023Review
- HIF‑1α and RACGAP1 promote the progression of hepatocellular carcinoma in a mutually regulatory way.Molecular medicine reports · 2023Article
- Identification of ATP6V0A4 as a potential biomarker in renal cell carcinoma using integrated bioinformatics analysis.Oncology letters · 2023Article
- High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer.Oncology reports · 2023Article
- Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.PloS one · 2023Article
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Detection and quantification of the vacuolar H+ATPase using the Legionella effector protein SidK.The Journal of cell biology · 2022Article
- Role of the prorenin receptor in endometrial cancer cell growth.Oncotarget · 2022Article
- The HAmerican journal of physiology. Cell physiology · 2021Review
- Endolysosomal TRPMLs in Cancer.Biomolecules · 2021Review
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Docosahexaenoic acid inhibits zymogen activation by suppressing vacuolar ATPase activation in cerulein-stimulated pancreatic acinar cells.Genes & nutrition · 2020Article
- Proton Pump Inhibitors Reduce Pancreatic Adenocarcinoma Progression by Selectively Targeting HCancers · 2020Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The vacuolar-ATPase (v-ATPase) is a proton transporter found on many intracellular organelles and the plasma membrane (PM). The v-ATPase on PMs of cancer cells may contribute to their invasive properties in vitro. Its relevance to human cancer tissues remains unclear. We investigated whether the expression and cellular localization of v-ATPase corresponded to the stage of human pancreatic cancer, and its effect on matrix metalloproteinase (MMP) activation in vitro. The intensity of v-ATPase staining increased significantly across the range of pancreatic histology from normal ducts to pancreatic intraepithelial neoplasms (PanIN), and finally pancreatic ductal adenocarcinoma (PDAC). Low-grade PanIN lesions displayed polarized staining confined to the basal aspect of the cell in the majority (86%) of fields examined. High-grade PanIN lesions and PDAC showed intense and diffuse v-ATPase localization. In pancreatic cancer cells, PM-associated v-ATPase colocalized with cortactin, a component of the leading edge that helps direct MMP release. Blockade of the v-ATPase with concanamycin or short-hairpin RNA targeting the V₁E subunit reduced MMP-9 activity; this effect was greatest in cells with prominent PM-associated v-ATPase. In cells with detectable MMP-2 activities, however, treatment with concanamycin markedly increased MMP-2's most activated forms. V-ATPase blockade inhibited functional migration and invasion in those cells with predominantly MMP-9 activity. These results indicate that human PDAC specimens show loss of v-ATPase polarity and increased expression that correlates with increasing invasive potential. Thus, v-ATPase selectively modulates specific MMPs that may be linked to an invasive cancer phenotype.
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