ArticleCell cycle (Georgetown, Tex.)2013
Carbonic anhydrase IX from cancer-associated fibroblasts drives epithelial-mesenchymal transition in prostate carcinoma cells.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82 citing papers in PubMed, 133 citations in OpenAlex.
- Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial.Journal of translational medicine · 2016Trial
- Single-Cell Transcriptomics Reveals Key Factors in Gastric Intestinal Metaplasia.Annals of surgical oncology · 2026Article
- Identification and Validation of Alkaliptosis Resistance-Associated Genes in Prostate Cancer Via Transcriptome Sequencing and Prediction of Biochemical Recurrence.Molecular biotechnology · 2026Article
- Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.Molecular oncology · 2025Article
- The role of exosomes in bladder cancer immunotherapy.Journal of the National Cancer Center · 2025Review
- Tumor perfusion enhancement by microbubbles ultrasonic cavitation reduces tumor glycolysis metabolism and alleviate tumor acidosis.Frontiers in oncology · 2024Article
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- New insights and options into the mechanisms and effects of combined targeted therapy and immunotherapy in prostate cancer.Molecular therapy oncolytics · 2023Review
- Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- A Hybrid Epithelial to Mesenchymal Transition in Ex Vivo Cutaneous Squamous Cell Carcinoma Tissues.International journal of molecular sciences · 2022Article
- Review
- Perfusion-Based Bioreactor Culture and Isothermal Microcalorimetry for Preclinical Drug Testing with the Carbonic Anhydrase Inhibitor SLC-0111 in Patient-Derived Neuroblastoma.International journal of molecular sciences · 2022Article
- The Epithelial-Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression.International journal of molecular sciences · 2022Review
- Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment.Sub-cellular biochemistry · 2022Article
- Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers.Frontiers in oncology · 2022Article
- Potentiality of Exosomal Proteins as Novel Cancer Biomarkers for Liquid Biopsy.Frontiers in immunology · 2022Review
- Role of pH Regulatory Proteins and Dysregulation of pH in Prostate Cancer.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Anti-breast cancer action of carbonic anhydrase IX inhibitor 4-[4-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-benzylidene-hydrazinocarbonyl]-benzenesulfonamide (BSM-0004):Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Article
- Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression.Cancers · 2021Article
22 more citing papers are in PubMed but not listed here.
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13 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Extracellular acidification, a mandatory feature of several malignancies, has been mainly correlated with metabolic reprogramming of tumor cells toward Warburg metabolism, as well as to the expression of carbonic anydrases or proton pumps by malignant tumor cells. We report herein that for aggressive prostate carcinoma, acknowledged to be reprogrammed toward an anabolic phenotype and to upload lactate to drive proliferation, extracellular acidification is mainly mediated by stromal cells engaged in a molecular cross-talk circuitry with cancer cells. Indeed, cancer-associated fibroblasts, upon their activation by cancer delivered soluble factors, rapidly express carbonic anhydrase IX (CA IX). While expression of CAIX in cancer cells has already been correlated with poor prognosis in various human tumors, the novelty of our findings is the upregulation of CAIX in stromal cells upon activation. The de novo expression of CA IX, which is not addicted to hypoxic conditions, is driven by redox-based stabilization of hypoxia-inducible factor-1. Extracellular acidification due to carbonic anhydrase IX is mandatory to elicit activation of stromal fibroblasts delivered metalloprotease-2 and -9, driving in cancer cells the epithelial-mesenchymal transition epigenetic program, a key event associated with increased motility, survival and stemness. Both genetic silencing and pharmacological inhibition of CA IX (with sulfonamide/sulfamides potent inhibitors) or metalloprotease-9 are sufficient to impede epithelial-mesenchymal transition and invasiveness of prostate cancer cells induced by contact with cancer-associated fibroblasts. We also confirmed in vivo the upstream hierarchical role of stromal CA IX to drive successful metastatic spread of prostate carcinoma cells. These data include stromal cells, as cancer-associated fibroblasts as ideal targets for carbonic anhydrase IX-directed anticancer therapies.
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