Affinage

CA9

Carbonic anhydrase 9 · UniProt Q16790

Length
459 aa
Mass
49.7 kDa
Annotated
2026-06-09
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CA9/CAIX is a hypoxia-induced, membrane-associated carbonic anhydrase that couples extracellular pH regulation to the metabolic and invasive adaptations of tumor cells (PMID:29965974, PMID:31723238). Its transcription is driven principally by HIF-1α acting with Sp1 and the co-activator CBP/p300 at the proximal CAIX promoter, a program rendered constitutive in clear cell renal cell carcinoma by VHL loss and normoxic HIF-1α accumulation; HIF-2α does not contribute (PMID:15184875). CAIX expression is additionally controlled by CpG methylation at the −74 bp promoter site, silencing being relieved by demethylation (PMID:11506497, PMID:10708480), and upstream regulators including EGFR/STAT3 (via HIF-1α stability) and the OTUB2–SNX29P2 axis converge on this HIF-1α/CA9 output (PMID:32823915, PMID:38701117). Catalytically, CAIX is highly efficient at low pH and shifts the CO₂/bicarbonate equilibrium to consume protons and stabilize the acidic tumor microenvironment (PMID:29965974). It works physically within transport metabolons: binding the SLC4 bicarbonate exchangers AE1/AE2/AE3 through its catalytic domain to enhance Cl⁻/HCO₃⁻ exchange (PMID:17652430), and binding the CD147-Ig1 domain to assemble with MCT1/MCT4 and facilitate proton-coupled lactate export, sustaining glycolysis and proliferation (PMID:31723238). Through pH control CAIX suppresses ferroptosis—its inhibition acidifies intracellular pH, raises ROS, and sensitizes cells to ferroptosis via AMPK/ACC1 signaling and synthetic lethality with NFS1 and xCT (PMID:34452919), and CA9 silencing enhances ferroptosis and radiosensitivity in glioma (PMID:37463506). CAIX silencing also reverses the Warburg phenotype by promoting mitochondrial biogenesis and ARG2-driven putrescine accumulation (PMID:32824856), and CAIX promotes migration and invasion through Rho-GTPase/ROCK signaling (PMID:21363891). Notably, impermeant catalytic inhibitors block extracellular pH regulation but fail to suppress cancer cell growth at relevant doses, indicating a non-catalytic contribution to CAIX's effects on tumor behavior (PMID:29965974, PMID:33523653).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Established that promoter DNA methylation, not only hypoxia, governs whether CA9 is expressed, explaining cell-line-specific silencing.

    Evidence Bisulfite sequencing of the MN/CA9 5' region with 5-aza-2'-deoxycytidine reactivation in RCC lines

    PMID:10708480

    Open questions at the time
    • Did not pinpoint the critical CpG site
    • Correlative methylation-expression link without functional promoter dissection
  2. 2001 Medium

    Localized methylation control to a single CpG at −74 bp, defining a discrete epigenetic switch for CA9 transcription.

    Evidence Luciferase reporters with in vitro methylated constructs and demethylation rescue in RCC cells

    PMID:11506497

    Open questions at the time
    • Methyl-CpG-binding factors mediating repression not identified
    • Single lab
  3. 2004 High

    Defined the core transcriptional machinery driving CA9, showing HIF-1α and Sp1 with CBP/p300 directly activate the promoter and that VHL loss makes this constitutive.

    Evidence DNase-I footprinting, EMSA, and promoter mutagenesis in ccRCC

    PMID:15184875

    Open questions at the time
    • HIF-2α role excluded but other context-specific regulators not surveyed
    • Did not address protein-level activity
  4. 2005 Medium

    Clarified that −74 bp methylation acts only as an accessory regulator outside RCC, operating under specific culture conditions rather than as the primary control.

    Evidence Bisulfite sequencing and demethylation under varied density/hypoxia in HeLa cells

    PMID:15754010

    Open questions at the time
    • Mechanism of density-dependent methylation effect unresolved
    • Single study
  5. 2007 High

    Demonstrated CAIX is not merely an enzyme but a structural scaffold, forming a bicarbonate transport metabolon with SLC4 exchangers via its catalytic domain.

    Evidence Reciprocal Co-IP, GST pull-down with domain deletions, and functional transport assays in HEK293

    PMID:17652430

    Open questions at the time
    • Whether the interaction requires catalytic activity not separated
    • Tumor relevance of the AE metabolon not tested
  6. 2011 Medium

    Connected CAIX to a motility/invasion program through Rho-GTPase signaling, beyond its metabolic role.

    Evidence Gain/loss-of-function with ROCK inhibitor and RhoA siRNA, microarray, and invasion assays in C33A cells

    PMID:21363891

    Open questions at the time
    • How CAIX activates RhoA/ROCK mechanistically not defined
    • Single lab, single cell line
  7. 2019 High

    Identified the MCT1/MCT4 lactate-transport metabolon assembled via CD147-Ig1 binding, showing metabolon disruption suppresses glycolysis and proliferation.

    Evidence Co-IP from patient breast tumor tissue and antibody-mediated metabolon disruption with lactate transport and proliferation readouts

    PMID:31723238

    Open questions at the time
    • In vivo therapeutic disruption not shown
    • Generality across tumor types not established
  8. 2020 Medium

    Showed CAIX silencing reverses the Warburg phenotype by inducing mitochondrial biogenesis and ARG2/putrescine accumulation while reducing adhesion proteins.

    Evidence siRNA knockdown with OXPHOS proteomics, metabolomics, surfaceomics, and migration assays in ccRCC

    PMID:32824856

    Open questions at the time
    • Causal chain from pH to mitochondrial biogenesis not dissected
    • Single lab
  9. 2020 Medium

    Defined a CAIX→LIN28/let-7 axis linking CAIX to glycolytic flux and stem-cell marker maintenance.

    Evidence Knockdown/knockout and overexpression with let-7 qRT-PCR and LIN28/PDK1/phospho-PDH/ALDH1/NANOG blots in breast cancer

    PMID:32560271

    Open questions at the time
    • Mechanism by which CAIX regulates LIN28 unknown
    • Single lab
  10. 2020 Medium

    Placed CAIX in the tumor immune microenvironment, regulating GBM motility and tumor-associated monocyte/macrophage behavior, with EGFR/STAT3 controlling its expression via HIF-1α.

    Evidence CAIX knockdown/overexpression with EGFR/STAT3 inhibition, HIF-1α stability, motility, and monocyte adhesion/polarization assays in GBM

    PMID:32823915

    Open questions at the time
    • Direct CAIX-dependent signal to monocytes not defined
    • Single lab
  11. 2021 High

    Established CAIX as a ferroptosis suppressor via pH/ROS control, with NFS1 and xCT as synthetic lethal partners acting through AMPK/ACC1.

    Evidence Genome-wide CRISPR synthetic lethal screen plus pH, ROS, AMPK/ACC1 readouts and in vivo tumor growth

    PMID:34452919

    Open questions at the time
    • Direct molecular link between bicarbonate and AMPK not fully resolved
    • Tissue specificity of synthetic lethality unclear
  12. 2021 Medium

    Quantified CAIX's superior low-pH catalytic efficiency yet showed catalytic inhibition alone is insufficient to block growth, first evidence for a non-catalytic function.

    Evidence pH-titration enzyme assays in membrane ghosts and impermeant sulfonamide (N-3500) treatment with growth/migration assays

    PMID:29965974

    Open questions at the time
    • Nature of the non-catalytic function not identified
    • Single lab
  13. 2021 High

    Reinforced the catalytic-vs-noncatalytic dissociation with a potent structurally-defined inhibitor that blocks pH regulation but barely affects cytotoxicity.

    Evidence Ki determination, thermal shift, crystal structure of SLC-149 bound to a CAIX-mimic, and cell growth/invasion assays

    PMID:33523653

    Open questions at the time
    • Structural basis of the non-catalytic scaffolding role not solved
    • In vivo efficacy not addressed
  14. 2023 Medium

    Showed CA9 silencing enhances X-ray-induced ferroptosis and radiosensitivity and triggers DAMP release in hypoxic glioma, extending the ferroptosis link to radiotherapy.

    Evidence siRNA knockdown with lipid peroxidation, iron-protein qPCR, clonogenic survival, and calreticulin immunofluorescence

    PMID:37463506

    Open questions at the time
    • Mechanism linking CA9 to iron regulation not resolved
    • Single lab
  15. 2024 Medium

    Identified post-transcriptional control of CA9 by the ZNF674-AS1/IGF2BP3 axis stabilizing CA9 mRNA to suppress pyroptosis and drive chemoresistance.

    Evidence RIP, CA9 mRNA stability assays, knockdown, and xenograft/pyroptosis assays in neuroblastoma

    PMID:38177154

    Open questions at the time
    • Whether IGF2BP3 directly recognizes CA9 mRNA modifications unclear
    • Single lab
  16. 2024 Medium

    Provided direct evidence of small-molecule target engagement with CA9 (vanillic acid) rewiring INSIG2/STIM1/SCAP–SREBP1–SCD1 to modulate ferroptosis in intestinal epithelium.

    Evidence CETSA and DARTS target engagement, INSIG2-STIM1/SCAP Co-IP, SREBP1 cleavage and SCD1 transcription with ferroptosis assays

    PMID:38438089

    Open questions at the time
    • How CA9 binding alters INSIG2 partner choice mechanistically unresolved
    • Single lab, non-tumor context

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of CAIX's catalytic-independent function—how the protein scaffold drives growth, invasion, and metabolon assembly beyond CO₂ hydration—remains unresolved.
  • Structural basis of the non-catalytic role not defined
  • Whether metabolon scaffolding requires catalytic activity untested
  • Mechanisms connecting CAIX to RhoA/ROCK and LIN28 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
AE1AE2AE3CD147IGF2BP3MCT1MCT4
Complex memberships
CAIX-AE bicarbonate transport metabolonCAIX-CD147-MCT1/MCT4 lactate transport metabolon

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 HIF-1α and Sp1, together with the co-activator CBP/p300, are critical transcriptional regulators of the CAIX (G250/MN) promoter in clear cell renal cell carcinoma. DNase-I footprint and band-shift assays demonstrated direct binding of HIF-1α and Sp1 to the CAIX promoter; mutations in the most proximal Sp1 or HIF-binding elements completely abolished promoter activity. HIF-2α showed no relationship with CAIX expression. Loss of VHL function leads to normoxic HIF-1α accumulation, which drives constitutive CAIX transcription in ccRCC. Transient transfection of promoter constructs, DNase-I footprint analysis, electrophoretic mobility shift assay (EMSA/band-shift), site-directed mutagenesis of promoter elements, Western blot correlation Oncogene High 15184875
2007 CAIX physically interacts with the SLC4 bicarbonate transporters AE1, AE2, and AE3 (but not SLC26A7) via its catalytic domain, forming a bicarbonate transport metabolon. Co-expression of CAIX increases AE2-mediated Cl⁻/HCO₃⁻ exchange activity by ~28%, and AE1/AE3 activity by ~32–37%, without altering transporter surface expression. CAIX and AE2 co-localize in human gastric mucosa. Co-immunoprecipitation, GST pull-down with domain-deletion constructs, functional transport assays in transfected HEK293 cells, co-immunofluorescence in human gastric tissue American Journal of Physiology. Cell Physiology High 17652430
2019 CAIX forms a transport metabolon with monocarboxylate transporters MCT1 and MCT4 in human breast cancer tissue (but not healthy breast tissue). The interaction requires binding of CAIX to the Ig1 domain of the MCT chaperone CD147. An antibody directed against the CD147-Ig1 domain displaces CAIX from MCT1/4 and suppresses CAIX-mediated facilitation of proton-coupled lactate transport, resulting in decreased lactate export, reduced glycolysis, and reduced cell proliferation in cancer cells. Co-immunoprecipitation from human breast cancer tissue and cell lines, antibody-mediated metabolon disruption, lactate transport assays, cell proliferation assays Oncogene High 31723238
2011 CA9 overexpression in human cervical carcinoma C33A cells induces cytoskeletal remodeling, disassembly of focal adhesions, weakened cell-cell adhesion, and increased cell motility and invasion. These effects are mediated through aberrant Rho-GTPase (RhoA/ROCK) signaling; inhibition of the Rho/ROCK pathway by Y-27632 or RhoA siRNA abrogated CA9-driven morphological and migratory changes. Silencing CA9 reversed these phenotypes. Gene transfection and siRNA knockdown, DNA microarray, immunofluorescence, Matrigel invasion assay, ROCK inhibitor treatment, si-RhoA knockdown Journal of Cell Science Medium 21363891
2001 Hypomethylation of a specific CpG site at −74 bp in the MN/CA9 promoter is associated with MN/CA9 gene expression in human renal cell carcinoma. In vitro CpG methylation of this site strongly suppresses promoter activity in a luciferase reporter assay, and treatment with the demethylating agent 5-aza-2'-deoxycytidine reactivates MN/CA9 expression in MN/CA9-negative RCC cell lines. Bisulfite genomic sequencing, luciferase promoter assay with in vitro methylated constructs, 5-aza-2'-deoxycytidine demethylation treatment, RT-PCR British Journal of Cancer Medium 11506497
2000 Hypomethylation of the 5′ region of the MN/CA9 gene correlates with its expression in renal cell carcinoma cell lines. Treatment of MN/CA9-negative RCC lines with the demethylating agent 5-aza-2'-deoxycytidine activates MN/CA9 gene expression, demonstrating that promoter methylation controls transcriptional silencing of CA9. Bisulfite genomic sequencing across seven CpG sites in the MN/CA9 5′ region, 5-aza-2'-deoxycytidine demethylation, RT-PCR Molecular Carcinogenesis Medium 10708480
2005 Methylation of a single CpG site at −74 bp in the CA9 promoter can down-modulate CA9 expression in non-RCC cancer cells (HeLa cervical carcinoma) specifically under high-density culture conditions, but not in sparse culture or under hypoxia. This indicates that promoter methylation acts as an accessory rather than primary regulatory mechanism for CA9 outside of RCC. Metabisulfite sequencing, 5-aza-2'-deoxycytidine demethylation, CA9 expression analysis under varying conditions International Journal of Oncology Medium 15754010
2021 A genome-wide synthetic lethal CRISPR screen identified NFS1 (an iron-sulfur cluster enzyme) and xCT (cystine transporter) as synthetic lethal partners of CAIX. CAIX inhibition acidifies intracellular pH, increases reactive oxygen species, and increases susceptibility to ferroptosis. Mechanistically, inhibiting CAIX-mediated bicarbonate production (or sodium-driven bicarbonate transport) while targeting xCT decreases AMPK activation and increases ACC1 activation, linking CAIX to regulation of lipid metabolism and ferroptosis resistance. Genome-wide CRISPR synthetic lethal screen, intracellular pH measurements, ROS assays, AMPK/ACC1 phosphorylation assays, tumor growth inhibition studies Science Advances High 34452919
2020 CA9 silencing in ccRCC cells upregulates oxidative phosphorylation-associated proteins and increases mitochondrial biogenesis, reversing the Warburg phenotype. CA9 knockdown also upregulates mitochondrial arginase 2 (ARG2), leading to accumulation of putrescine that suppresses cell proliferation. Additionally, surface proteomics after CA9 knockdown revealed downregulation of ECM-receptor interaction and cell adhesion proteins, causing decreased cell migration. siRNA knockdown, OXPHOS protein profiling, mitochondrial biogenesis assays, surfaceomics (surface protein mass spectrometry), cell migration assays, metabolomics International Journal of Molecular Sciences Medium 32824856
2020 CAIX downregulation in breast cancer cells under hypoxia leads to increased levels of let-7 miRNA family members and decreased LIN28 protein. Reduced LIN28 downstream leads to decreased PDK1 expression and decreased phosphorylation of pyruvate dehydrogenase (PDH) at Ser-232, attenuating glycolysis. Conversely, CAIX overexpression enhances LIN28, ALDH1, and NANOG levels. This identifies a CAIX→LIN28/let-7 axis linking CAIX to glycolytic metabolism and cancer stem cell marker maintenance. siRNA knockdown and CRISPR knockout, CAIX overexpression, qRT-PCR for let-7 miRNAs, Western blot for LIN28/PDK1/phospho-PDH/ALDH1/NANOG International Journal of Molecular Sciences Medium 32560271
2020 CAIX regulates GBM cell motility, monocyte adhesion to GBM cells, and polarization of tumor-associated monocytes/macrophages under hypoxic conditions. EGFR/STAT3 signaling was shown to regulate CAIX expression under hypoxia by affecting HIF-1α stability. Knockdown of CAIX abrogated hypoxia-induced GBM motility changes and monocyte adhesion. CAIX knockdown and overexpression in GBM cell lines, EGFR/STAT3 pathway inhibition, HIF-1α stability assays, cell motility assays, monocyte adhesion assays, macrophage polarization assays International Journal of Molecular Sciences Medium 32823915
2018 SOX9 transcriptionally regulates CA9 expression in glioblastoma cells; SOX9 knockdown via lentiviral infection leads to downregulation of both SOX9 and CA9, with downstream decrease in Akt phosphorylation, decreased BCL-2, and increased BAX. Pharmacological inhibition of CA9 with U-104 in combination with TMZ induces glioma cell death, with similar pathway changes, establishing a SOX9/CA9/Akt axis linked to chemoresistance. Lentiviral SOX9 knockdown, gene microarray, Western blot, RT-qPCR, CA9 inhibitor (U-104) treatment, cell death assays International Journal of Oncology Low 29749469
2021 PADI4 upregulates CA9 expression in esophageal squamous cell carcinoma cells. PCR array analysis showed increased CA9 mRNA upon PADI4 overexpression and decreased CA9 upon PADI4 siRNA knockdown. PADI4 and CA9 co-localize in ESCC tissues, and PADI4-driven CA9 upregulation contributes to tumor growth in vivo. Lentiviral PADI4 overexpression and siRNA knockdown, PCR array, Western blot, immunohistochemistry co-localization, xenograft mouse model Molecular Carcinogenesis Low 30242913
2024 Vanillic acid (VA) directly binds CA9 (identified by CETSA and DARTS assays). VA binding to CA9 causes INSIG2 to interact with STIM1 instead of SCAP, redirecting SCAP-SREBP1 from ER retention to Golgi translocation and cleavage into mature SREBP1. Activated SREBP1 then induces transcription of SCD1, which inhibits ferroptosis in intestinal epithelial cells. CETSA (cellular thermal shift assay), DARTS (drug affinity responsive target stability) assay, protein co-immunoprecipitation (INSIG2-STIM1 and SCAP), SREBP1 cleavage assay, SCD1 transcription analysis, ferroptosis assays Pharmacological Research Medium 38438089
2024 OTUB2 silencing in ovarian cancer cells leads to destabilization of SNX29P2, which prevents VHL-mediated degradation of HIF-1α. Elevated HIF-1α then activates CA9 transcription, driving glycolysis and chemoresistance. Pharmacological inhibition of CA9 suppresses tumor growth and synergizes with carboplatin in OTUB2-silenced ovarian cancer models. siRNA knockdown, Western blot for HIF-1α/VHL/CA9 pathway, CA9 inhibitor treatment, tumor growth assays, carboplatin combination treatment Proceedings of the National Academy of Sciences USA Medium 38701117
2021 CAIX inhibitory activity at low pH is more catalytically efficient than CAXII. pH titration assays of membrane ghosts showed significant differences in catalytic efficiency and pKa values between CAIX and CAXII. CAIX shifts the equilibrium between CO2 and bicarbonate in favor of CO2 production by consuming protons in the acidic tumor microenvironment, supporting an extracellular pH-stabilizing role for cancer cell survival. However, an impermeant sulfonamide inhibitor (N-3500) that blocks CAIX catalytic activity was insufficient to inhibit cell growth at relevant concentrations, suggesting a noncatalytic function also contributes to CAIX effects on tumor cell behavior. Enzymatic activity assays (pH titration in membrane ghosts), sulfonamide inhibitor (N-3500) treatment, siRNA knockdown, cell growth and migration assays PloS One Medium 29965974
2021 SLC-149 inhibits CAIX catalytic activity with greater potency than acetazolamide. Structural analysis (crystal structure of SLC-149 bound to a CAIX-mimic) and thermal stabilization assays explain binding preferences. However, despite inhibiting extracellular pH regulation, SLC-149 has minimal effect on cancer cell cytotoxicity and requires high concentrations to inhibit growth, migration, and invasion, supporting the hypothesis that CAIX's role in controlling cell growth is at least partly independent of its carbonic anhydrase catalytic activity. Enzyme inhibition assays (Ki determination), thermal shift assay, crystal structure of inhibitor bound to CAIX-mimic, cell culture cytotoxicity, cell growth/migration/invasion assays Journal of Medicinal Chemistry High 33523653
2024 ZNF674-AS1 lncRNA interacts with the RNA-binding protein IGF2BP3 to enhance stability of CA9 mRNA by binding to the CA9 transcript, elevating CA9 protein expression. This CA9 upregulation suppresses cisplatin-induced pyroptosis and promotes cell proliferation in neuroblastoma. Targeting ZNF674-AS1 or CA9 suppresses tumor growth in vivo and restores cisplatin sensitivity. RNA immunoprecipitation (RIP) for ZNF674-AS1–IGF2BP3 interaction, CA9 mRNA stability assay, CA9 knockdown, in vivo xenograft tumor growth, pyroptosis assays, cell proliferation assays Cell Death & Disease Medium 38177154
2023 CA9 knockdown in hypoxic glioma cells significantly alters iron regulation-related protein expression and enhances X-ray-induced ferroptosis and radiosensitivity. CA9 silencing overcomes hypoxic ferroptosis resistance, and enhancing ferroptosis by CA9 knockdown promotes exposure and release of damage-associated molecular patterns (DAMPs). siRNA knockdown, X-ray irradiation, lipid peroxidation assay (C11-BODIPY staining), RT-qPCR for ferroptosis markers and iron-associated proteins, clonogenic survival assay, immunofluorescence for calreticulin (DAMPs) International Journal of Radiation Biology Medium 37463506

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Molecular therapy : the journal of the American Society of Gene Therapy 589 23423337
1997 Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer research 228 9230182
2003 GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. British journal of cancer 188 14520462
2003 GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding. International journal of cancer 187 12532423
2011 Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4. BMC cancer 180 21569415
2021 A Carbonic Anhydrase IX (CAIX)-Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti-Tumor Immunity. Angewandte Chemie (International ed. in English) 179 34842317
2009 The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy. British journal of cancer 164 19165203
2004 Strict regulation of CAIX(G250/MN) by HIF-1alpha in clear cell renal cell carcinoma. Oncogene 154 15184875
2016 Treatment of metastatic renal cell carcinoma (mRCC) with CAIX CAR-engineered T-cells-a completed study overview. Biochemical Society transactions 136 27284065
2011 Carbonic anhydrase IX (CA9) modulates tumor-associated cell migration and invasion. Journal of cell science 111 21363891
2007 Interactions of transmembrane carbonic anhydrase, CAIX, with bicarbonate transporters. American journal of physiology. Cell physiology 110 17652430
2021 Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors. Science advances 108 34452919
2020 CAIX-specific CAR-T Cells and Sunitinib Show Synergistic Effects Against Metastatic Renal Cancer Models. Journal of immunotherapy (Hagerstown, Md. : 1997) 89 31574023
2010 HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression. BMC cancer 86 21050481
2023 Nanomedicines Reprogram Synovial Macrophages by Scavenging Nitric Oxide and Silencing CA9 in Progressive Osteoarthritis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 83 36748885
2009 Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development. BMC developmental biology 78 19291313
2010 Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX. Virchows Archiv : an international journal of pathology 76 20526721
2016 Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O2 Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia. Molecular imaging and biology 70 26276155
2003 Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma. Journal of medical genetics 70 12676895
2014 Carbonic anhydrase IX (CAIX) as a mediator of hypoxia-induced stress response in cancer cells. Sub-cellular biochemistry 63 24146383
2019 Targeting hypoxia downstream signaling protein, CAIX, for CAR T-cell therapy against glioblastoma. Neuro-oncology 61 31276594
2018 Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness. Metabolites 60 29439394
2015 Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo. Molecular cancer 55 26062742
2001 Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma. British journal of cancer 54 11506497
2024 Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis. Pharmacological research 52 38438089
2016 [64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma. Oncotarget 52 27437764
2018 Differential expression and function of CAIX and CAXII in breast cancer: A comparison between tumorgraft models and cells. PloS one 51 29965974
2013 ImmunoPET imaging of renal cell carcinoma with (124)I- and (89)Zr-labeled anti-CAIX monoclonal antibody cG250 in mice. Cancer biotherapy & radiopharmaceuticals 49 23697926
2021 Design, synthesis and biological evaluation of sulfamoylphenyl-quinazoline derivatives as potential EGFR/CAIX dual inhibitors. European journal of medicinal chemistry 47 33640672
2020 Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes. Histopathology 46 32639054
2013 Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including acetazolamide in human glioblastoma. Bioorganic & medicinal chemistry 46 23706268
2020 Carbonic anhydrase 9 (CA9) expression in non-small-cell lung cancer: correlation with regulatory FOXP3+T-cell tumour stroma infiltration. British journal of cancer 45 32066909
2018 Blocking HIF signaling via novel inhibitors of CA9 and APE1/Ref-1 dramatically affects pancreatic cancer cell survival. Scientific reports 45 30214007
2016 Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization. EJNMMI research 45 26860296
2012 Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast cancer research and treatment 44 22976806
2019 CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells. Oncogene 43 31723238
2024 Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects. Molecular cancer 42 38491381
2015 [(18)F]VM4-037 MicroPET Imaging and Biodistribution of Two In Vivo CAIX-Expressing Tumor Models. Molecular imaging and biology 42 25708744
2023 Oncolytic adenovirus-mediated expression of CCL5 and IL12 facilitates CA9-targeting CAR-T therapy against renal cell carcinoma. Pharmacological research 41 36796464
2020 CAIX-Mediated Control of LIN28/let-7 Axis Contributes to Metabolic Adaptation of Breast Cancer Cells to Hypoxia. International journal of molecular sciences 39 32560271
2011 Diagnostic use of PAX8, CAIX, TTF-1, and TGB in metastatic renal cell carcinoma of the thyroid. The American journal of surgical pathology 39 21451364
2018 Association between SOX9 and CA9 in glioma, and its effects on chemosensitivity to TMZ. International journal of oncology 36 29749469
2014 Upregulation of Claudin-4, CAIX and GLUT-1 in distant breast cancer metastases. BMC cancer 34 25417118
2020 Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness. International journal of molecular sciences 33 32340282
2021 Oncolytic adenovirus-mediated expression of decorin facilitates CAIX-targeting CAR-T therapy against renal cell carcinoma. Molecular therapy oncolytics 32 34977339
2013 Carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up. BJU international 32 23551810
2010 Clear cell meningioma: a clinicopathologic study of 18 tumors and examination of the use of CD10, CA9, and RCC antibodies to distinguish between clear cell meningioma and metastatic clear cell renal cell carcinoma. Applied immunohistochemistry & molecular morphology : AIMM 32 20453815
2007 Circulating oncoproteins HER2/neu, EGFR and CAIX (MN) as novel cancer biomarkers. Expert review of molecular diagnostics 32 17489737
2019 CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models. Scientific reports 31 31827111
2012 Impacts of CA9 gene polymorphisms and environmental factors on oral-cancer susceptibility and clinicopathologic characteristics in Taiwan. PloS one 31 23226559
2017 Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation. Oncotarget 30 28099149
2021 Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model. Molecular therapy oncolytics 28 35118195
2018 Aberrant expression of membranous carbonic anhydrase IX (CAIX) is associated with unfavorable disease course in papillary and clear cell renal cell carcinoma. Urologic oncology 28 30322727
2009 Soluble form of carbonic anhydrase IX (CAIX) in transitional cell carcinoma of urinary tract. Neoplasma 28 19473055
2013 Dendritic cell-based immunotherapy in prevention and treatment of renal cell carcinoma: efficacy, safety, and activity of Ad-GM·CAIX in immunocompetent mouse models. Journal of immunotherapy (Hagerstown, Md. : 1997) 26 23377663
2012 Proteomic profiling of the 11-dehydrosinulariolide-treated oral carcinoma cells Ca9-22: effects on the cell apoptosis through mitochondrial-related and ER stress pathway. Journal of proteomics 26 22885288
2009 The tumor antigens RHAMM and G250/CAIX are expressed in head and neck squamous cell carcinomas and elicit specific CD8+ T cell responses. International journal of oncology 26 19212667
2008 Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer. Biomarker insights 26 19578493
2024 OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. Proceedings of the National Academy of Sciences of the United States of America 25 38701117
2021 Inhibition of Carbonic Anhydrase Using SLC-149: Support for a Noncatalytic Function of CAIX in Breast Cancer. Journal of medicinal chemistry 25 33523653
2016 Sinuleptolide inhibits proliferation of oral cancer Ca9-22 cells involving apoptosis, oxidative stress, and DNA damage. Archives of oral biology 25 26954095
2016 Prophylactic irradiation of para-aortic lymph nodes for patients with locally advanced cervical cancers with and without high CA9 expression (KROG 07-01): A randomized, open-label, multicenter, phase 2 trial. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 25 27102843
2014 Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 affibody molecule. International journal of oncology 25 25434612
2023 The relationship between carbonic anhydrase IX (CAIX) and patient survival in breast cancer: systematic review and meta-analysis. Diagnostic pathology 24 37061698
2020 In vitro and in vivo BNCT investigations using a carborane containing sulfonamide targeting CAIX epitopes on malignant pleural mesothelioma and breast cancer cells. Scientific reports 24 33159147
2022 CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer. Frontiers in oncology 23 35155218
2014 Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor. Molecular therapy oncolytics 23 27119093
2010 Taiwan cobra cardiotoxin III inhibits Src kinase leading to apoptosis and cell cycle arrest of oral squamous cell carcinoma Ca9-22 cells. Toxicon : official journal of the International Society on Toxinology 23 20493203
2023 Cu(ii)-BODIPY photosensitizer for CAIX overexpressed cancer stem cell therapy. Chemical science 22 36819853
2020 CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions. International journal of molecular sciences 22 32823915
2013 Response of CAIX and CAXII to in vitro re-oxygenation and clinical significance of the combined expression in NSCLC patients. Lung cancer (Amsterdam, Netherlands) 22 23910904
2012 Co-expression of VEGF and CA9 in ovarian high-grade serous carcinoma and relationship to survival. Virchows Archiv : an international journal of pathology 22 22699808
2011 The expression of the hypoxia markers CA9 and CXCR4 is correlated with survival in patients with neuroendocrine tumours of the ileum. Neuroendocrinology 22 22133596
2000 Activation of the MN/CA9 gene is associated with hypomethylation in human renal cell carcinoma cell lines. Molecular carcinogenesis 22 10708480
2021 Artemisinin protects DPSC from hypoxia and TNF-α mediated osteogenesis impairments through CA9 and Wnt signaling pathway. Life sciences 21 33811898
2014 Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study. Neoplasma 21 24471939
2005 Methylation of the CA9 promoter can modulate expression of the tumor-associated carbonic anhydrase IX in dense carcinoma cell lines. International journal of oncology 21 15754010
2023 The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs. Cancer letters 20 37549770
2024 LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma. Cell death & disease 19 38177154
2018 Quantitative Imaging of the Hypoxia-Related Marker CAIX in Head and Neck Squamous Cell Carcinoma Xenograft Models. Molecular pharmaceutics 19 30550290
2018 Synthesis and biological investigation of new carbonic anhydrase IX (CAIX) inhibitors. Chemico-biological interactions 18 29454615
2018 PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up-regulates CA9 expression. Molecular carcinogenesis 18 30242913
2018 CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients. Head and neck pathology 18 30291511
2025 Cancer Specific CAIX-Targeting Supramolecular Lysosome-Targeting Chimeras (Supra-LYTAC) for Targeted Protein Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 40178177
2016 New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs. European journal of medicinal chemistry 17 27823879
2024 Towards effective CAIX-targeted radionuclide and checkpoint inhibition combination therapy for advanced clear cell renal cell carcinoma. Theranostics 16 38948062
2020 Expression of CA2 and CA9 carbonic anhydrases in ulcerative colitis and ulcerative colitis-associated colorectal cancer. Pathology international 16 32410301
2019 Comparative evaluation of affibody- and antibody fragments-based CAIX imaging probes in mice bearing renal cell carcinoma xenografts. Scientific reports 16 31624303
2023 Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth. Chemical science 15 37293644
2021 Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity. Molecular therapy oncolytics 15 34977338
2013 Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan. PloS one 15 24349364
2022 Novel VHH-Based Tracers with Variable Plasma Half-Lives for Imaging of CAIX-Expressing Hypoxic Tumor Cells. Molecular pharmaceutics 14 35044182
2013 The Expression of Glut-1, CAIX, and MCT4 in Mucinous Carcinoma. Journal of breast cancer 14 23843845
2007 MN/CA9: a potential gene marker for detection of malignant cells in effusions. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 14 17536770
2023 CA9 knockdown enhanced ionizing radiation-induced ferroptosis and radiosensitivity of hypoxic glioma cells. International journal of radiation biology 13 37463506
2019 CAIX is a predictor of pathological complete response and is associated with higher survival in locally advanced breast cancer submitted to neoadjuvant chemotherapy. BMC cancer 13 31795962
2016 The Sulfamate Small Molecule CAIX Inhibitor S4 Modulates Doxorubicin Efficacy. PloS one 13 27513947
2021 Effects and Related Mechanisms of the Senolytic Agent ABT-263 on the Survival of Irradiated A549 and Ca9-22 Cancer Cells. International journal of molecular sciences 12 34948029
2020 CA9 Silencing Promotes Mitochondrial Biogenesis, Increases Putrescine Toxicity and Decreases Cell Motility to Suppress ccRCC Progression. International journal of molecular sciences 12 32824856
2015 The In Vitro and In Vivo Activity of the Microtubule Disruptor STX140 Is Mediated by Hif-1 Alpha and CAIX Expression. Anticancer research 12 26408684

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