Affinage

FOLH1

Glutamate carboxypeptidase 2 · UniProt Q04609

Length
750 aa
Mass
84.3 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOLH1 (also known as PSMA/GCPII) is a type II transmembrane glycoprotein that functions as a dual-specificity metallopeptidase, catalyzing both the hydrolysis of N-acetylaspartylglutamate (NAAG) to N-acetylaspartate and glutamate in the nervous system (NAALADase activity) and the sequential removal of gamma-linked glutamates from folylpolyglutamates (folate hydrolase activity) (PMID:9694964, PMID:11210180). In the brain, its NAALADase activity regulates extracellular glutamate levels and NAAG signaling, and pharmacological inhibition with 2-PMPA is neuroprotective in ischemia models (PMID:10581082); in the intestinal mucosa, elevated FOLH1 activity contributes to inflammatory bowel disease pathology, as demonstrated by resistance of Folh1-knockout mice to experimental colitis (PMID:27536732). Prostate-selective expression is driven by an intronic enhancer (PSME) repressed by androgen receptor signaling and the transcription factor Sox7, while surface density is modulated by filamin A-mediated retention in recycling endosomes and clathrin-dependent internalization (PMID:11350116, PMID:30488457, PMID:12750292). Expression heterogeneity in prostate cancer is governed by reversible epigenetic silencing through CpG methylation and H3K27 deacetylation at the FOLH1 locus, and by neuroendocrine lineage transitions that suppress FOLH1 transcription (PMID:36821396, PMID:30400059).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Establishing where NAALADase protein resides in vivo resolved that this enzyme acts extracellularly in brain neuropil and at the kidney brush border, consistent with a role in catabolism of extracellular substrates.

    Evidence Immunocytochemistry with specific anti-NAALADase antiserum in rat brain and kidney sections

    PMID:1545010

    Open questions at the time
    • Prostate expression not yet linked to the same gene product
    • Substrate access and regulation of activity in situ unknown
  2. 1998 High

    Demonstrating that brain NAALADase and prostate PSMA are the same gene product unified two fields and established FOLH1 as a single gene encoding both enzymatic activities in distinct tissues.

    Evidence Kinetic enzyme assays, Northern blots, RT-PCR cloning, and immunoprecipitation with anti-PSMA mAb 7E11-C5 capturing 82% of cerebellar NAALADase activity

    PMID:9694964

    Open questions at the time
    • Tissue-specific transcriptional regulation not yet characterized
    • Structural basis for dual enzymatic activities unknown
  3. 1999 High

    Defining PSMA domain topology on viable cells and its expression in tumor-associated neovasculature established the protein as a surface-accessible target in cancer and revealed an unexpected non-prostate expression pattern.

    Evidence Immunohistochemistry with five monoclonal antibodies targeting distinct PSMA epitopes on viable cells and fresh-frozen tumor tissues; CD34 co-staining

    PMID:10397265

    Open questions at the time
    • Mechanism driving neovascular expression unresolved
    • Functional role of PSMA in endothelial cells unknown
  4. 1999 High

    Pharmacological inhibition of NAALADase with 2-PMPA established that FOLH1 enzymatic activity directly controls extracellular glutamate levels and that its inhibition is neuroprotective, providing the first functional consequence of FOLH1 catalysis in vivo.

    Evidence In vitro neuronal ischemia model and in vivo rat MCAO with microdialysis measurement of glutamate and NAAG

    PMID:10581082

    Open questions at the time
    • Genetic loss-of-function confirmation in brain not shown
    • Downstream signaling pathways from glutamate release not dissected
  5. 2001 High

    Identification of the PSME intronic enhancer and its androgen-mediated repression explained how FOLH1 achieves prostate-selective expression and why androgen deprivation upregulates PSMA, a key clinical observation.

    Evidence Enhancer trap assay, luciferase reporters in prostate/non-prostate lines, androgen treatment experiments

    PMID:11350116

    Open questions at the time
    • Transcription factors binding PSME not identified
    • Chromatin architecture at enhancer-promoter loop not mapped
  6. 2001 High

    Reconstitution of mouse Folh1 confirmed functional conservation of both NAALADase and folate hydrolase activities, validating the mouse as a model for FOLH1 biology.

    Evidence Transfection of Folh1 cDNA into cells with enzymatic activity assays for both NAALADase and folate hydrolase

    PMID:11210180

    Open questions at the time
    • Physiological importance of folate hydrolase activity in vivo not tested
  7. 2003 High

    Discovery that filamin A interacts with the PSMA cytoplasmic tail and retains it in recycling endosomes provided the first mechanism for post-translational regulation of PSMA surface density and enzymatic activity.

    Evidence Co-immunoprecipitation, comparison of filamin-positive vs. filamin-negative isogenic cell lines, NAALADase activity assays, subcellular fractionation

    PMID:12750292

    Open questions at the time
    • Structural basis of filamin A–PSMA interaction not mapped at residue level
    • In vivo relevance of filamin A regulation not established
  8. 2016 High

    Genetic knockout and pharmacological inhibition in multiple colitis models established FOLH1 enzymatic activity as a pathogenic driver of intestinal inflammation, extending its functional significance beyond the nervous system.

    Evidence FOLH1-knockout mice resistant to DSS colitis; 2-PMPA ameliorates disease in DSS and IL-10−/− models; elevated GCPII activity in IBD patient specimens

    PMID:27536732 PMID:28159515

    Open questions at the time
    • Substrate (NAAG or folate) mediating intestinal pathology not identified
    • Cell type expressing FOLH1 in gut mucosa not resolved
  9. 2016 High

    Conditioned media and co-implantation experiments demonstrated that tumor cell-secreted factors are sufficient to induce PSMA expression on endothelial cells, explaining the neovascular PSMA expression seen across solid tumors.

    Evidence Cancer cell-conditioned media treatment of HUVECs in vitro; HUVEC–cancer cell co-implantation in mice with J591 internalization readout

    PMID:27458033

    Open questions at the time
    • Identity of the inducing factor(s) not determined
    • Signaling pathway in endothelial cells not characterized
  10. 2018 High

    Identification of Sox7 as a direct transcriptional repressor binding PSME resolved a specific trans-acting factor controlling PSMA expression, with its NLS but not β-catenin interaction required for repression.

    Evidence ChIP, EMSA, luciferase reporters, stable Sox7 expression in prostate cancer lines, domain mutagenesis

    PMID:30488457

    Open questions at the time
    • Other transcription factors binding PSME not systematically identified
    • Sox7 regulation in prostate cancer progression unknown
  11. 2018 Medium

    Neuroendocrine differentiation was shown to suppress FOLH1 expression, linking lineage plasticity to loss of PSMA and resistance to AR-targeted therapy, a clinically important escape mechanism.

    Evidence Transcript analysis of 909 tumors, NE-induced cell models with p53 loss, 18 NEPC PDX models

    PMID:30400059

    Open questions at the time
    • Direct transcriptional mechanism of NE-driven FOLH1 suppression not dissected
    • Whether PSMA loss is cause or consequence of NE phenotype unclear
  12. 2023 High

    Epigenetic profiling revealed that PSMA-negative prostate tumors acquire CpG methylation and lose H3K27ac at the FOLH1 locus, and that HDAC inhibitors restore PSMA expression, establishing a reversible epigenetic silencing mechanism.

    Evidence ChIP-seq, DNA methylation analysis, HDAC inhibitor treatment in cell lines and xenografts, multi-site autopsy sampling

    PMID:36821396

    Open questions at the time
    • Specific HDAC isoforms responsible not identified
    • Durability of epigenetic re-expression in patients not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of tumor-secreted factors that induce PSMA on neovasculature, the substrate mediating FOLH1's pathogenic role in colitis, and the complete set of transcription factors governing tissue-specific FOLH1 expression remain unresolved.
  • Paracrine inducer of neovascular PSMA not identified
  • NAAG vs. folate substrate relevance in gut inflammation not determined
  • Full enhancer-promoter looping architecture at FOLH1 locus not mapped in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 7 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-112316 Neuronal System 3
Partners
FLNASOX7

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PSMA (FOLH1) is a type II integral membrane glycoprotein expressed on the surface of prostate cancer cells and in tumor-associated neovasculature of a wide spectrum of malignant neoplasms; antibodies to the extracellular domain (J591, J415) bind viable prostate cancer cells whereas antibodies to the intracellular domain (7E11) do not, establishing domain topology and accessibility. Immunohistochemistry with five distinct anti-PSMA monoclonal antibodies on viable cell lines and fresh-frozen tissue; CD34 co-staining for endothelial confirmation Cancer research High 10397265
2004 PSMA has two enzymatic activities—folate hydrolase (gamma-glutamyl carboxypeptidase) and NAALADase (N-acetylated alpha-linked acidic dipeptidase)—and undergoes internalization via clathrin-coated pits, consistent with receptor recycling behavior. Review consolidating enzymatic activity assays and prior internalization studies Journal of cellular biochemistry High 14755683
2001 The mouse homolog of PSMA (Folh1) encodes a glutamate-preferring carboxypeptidase with both NAALADase and folate hydrolase activities; cells transfected with Folh1 gained both enzymatic activities, confirming the functional equivalence of mouse Folh1 and human PSMA/FOLH1. cDNA cloning, transfection-based enzymatic activity assays (NAALADase and folate hydrolase), FISH chromosomal mapping, tissue expression analysis Mammalian genome High 11210180
1999 NAALADase (FOLH1/GCPII) hydrolyzes NAAG to N-acetylaspartate and glutamate; selective inhibition with 2-PMPA reduces extracellular glutamate, increases NAAG, and is neuroprotective in ischemic models, establishing the enzyme's role in glutamate homeostasis in the brain. In vitro neuronal culture stroke model; in vivo rat transient middle cerebral artery occlusion; microdialysis measurement of extracellular glutamate and NAAG Nature medicine High 10581082
1992 NAALADase (FOLH1) protein is localized to neuropil (not neuronal cytoplasm) in rat brain regions enriched in NAAG, and to the brush border of proximal convoluted tubules in kidney, consistent with its role in extracellular NAAG catabolism. Immunocytochemistry with specific anti-NAALADase antiserum in rat brain and kidney sections The Journal of comparative neurology High 1545010
1998 Brain NAALADase and prostate PSMA (FOLH1) are the same enzyme: they share identical kinetic profiles, pharmacological sensitivities, common mRNA splice forms (2.8-, 4.0-, and 6.0-kb species), and the anti-PSMA mAb 7E11-C5 immunoprecipitates 82% of cerebellar NAALADase activity. Kinetic enzyme assays, Northern hybridization, RT-PCR cloning of cerebellar cDNA, immunoprecipitation with anti-PSMA antibody The Journal of pharmacology and experimental therapeutics High 9694964
2003 Filamin A, an actin cross-linking protein, associates with the cytoplasmic tail of PSMA; this interaction localizes PSMA to the recycling endosomal compartment, reduces its internalization rate, and decreases its NAALADase activity. Co-immunoprecipitation, ectopic PSMA expression in filamin-negative vs. filamin-positive cell lines, NAALADase activity assays, subcellular fractionation/localization Cancer research High 12750292
2001 A tissue-specific enhancer (PSME) located in the third intron (~12 kb downstream of the transcription start) of the FOLH1 gene drives prostate-selective expression; it contains a 72-bp direct repeat, activates transcription >250-fold in LNCaP cells, and its activity is repressed by androgen, mirroring regulation of the endogenous gene. Enhancer trap assay with overlapping genomic DNA fragments, luciferase reporter assays in prostate and non-prostate cell lines, androgen treatment experiments Genomics High 11350116
2016 FOLH1/GCPII enzymatic activity is elevated 2.8- to 41-fold in the affected intestinal mucosa of IBD patients; pharmacological inhibition of this activity with 2-PMPA ameliorates disease in DSS colitis and IL-10−/− mouse models, and FOLH1 knockout mice are resistant to DSS-induced colitis. Enzymatic activity quantification in surgical specimens, two murine IBD models (DSS colitis and IL-10−/− spontaneous colitis), genetic knockout, pharmacological inhibition with 2-PMPA JCI insight High 27536732
2016 Cancer cell-conditioned media induces PSMA expression in human umbilical vein endothelial cells (HUVECs) in vitro, and cancer cell co-implantation induces PSMA expression in HUVECs in vivo; PSMA-induced HUVECs can internalize the anti-PSMA mAb J591 and PSMA-binding ligand nanoparticles, demonstrating that tumor cell crosstalk drives neovascular PSMA expression. Conditioned media experiments, HUVEC-cancer cell co-implantation mouse model, internalization assays with fluorescent-labeled J591 mAb and nanoparticles Molecular cancer research High 27458033
2018 Neuroendocrine differentiation of prostate cancer suppresses FOLH1/PSMA expression; PSMA suppression is associated with loss of p53 and NE induction, and PSMA-suppressed cells show increased colony formation and resistance to enzalutamide. Transcript analysis across 909 tumors, NE-induced cell line models with hormone depletion and p53 loss, flow cytometry for protein expression, 18 NEPC patient-derived xenograft models Endocrine-related cancer Medium 30400059
2023 PSMA (FOLH1) expression heterogeneity in metastatic castration-resistant prostate cancer is mediated by reversible epigenetic mechanisms: PSMA-negative tumors show gain of CpG methylation and loss of H3K27 acetylation at the FOLH1 locus; HDAC inhibitor treatment restores PSMA expression in vitro and in vivo. ChIP-seq for H3K27ac, DNA methylation analysis, HDAC inhibitor treatment in cell lines and xenograft models, autopsy cohort multi-site sampling JCI insight High 36821396
2018 Sox7 negatively regulates PSMA expression by directly binding to the PSMA enhancer (PSME) through SOX box sites #2 and #4; the nuclear localization sequences (NLS) but not the β-catenin interaction motif of Sox7 are required for this repression. ChIP assay, EMSA, luciferase reporter assay, stable Sox7 expression in LNCaP/C4-2 and 22Rv1 cells, Sox7 domain mutant analysis The Prostate High 30488457
2003 Mouse Folh1 (PSMA homolog) is expressed at highest levels in kidney and brain (not in prostate tumor in TRAMP mice); folate hydrolase activity in tissues parallels Folh1 mRNA expression, confirming the enzyme's tissue-specific catalytic activity. Real-time quantitative PCR, folate hydrolase activity assays in multiple tissues of TRAMP and control mice The Prostate Medium 12712410
2024 PSMA expression is regulated by a transcription complex that acts on the FOLH1 promoter via a looping upstream enhancer, intergenic enhancers, and differentially methylated regions; PSMA suppression mechanisms include lineage plasticity, tumor microenvironment, and epigenetic silencing. Review integrating ChIP, DNA methylation, and enhancer-looping data from prior molecular studies Nature reviews. Urology Medium 38977769
2021 Androgen receptor blockade by enzalutamide increases PSMA expression in PSMA-low prostate cancer cell lines (22Rv1) 2.2-fold and in PSMA-high lines (C4-2, LNCaP) ~2.3–2.6-fold; this is confirmed in vivo by 68Ga-PSMA PET in a xenograft model and in an mCRPC patient. Flow cytometry, immunohistochemistry, 68Ga-PSMA PET/CT in NOD/Scid xenograft mouse model, clinical case International journal of molecular sciences Medium 34299051
1996 PSMA functions as both a neurocarboxypeptidase and a membrane folate hydrolase; an alternatively spliced form, PSM', localizes to the cytoplasm in normal prostate, while PSMA itself is a type II membrane protein. Biochemical characterization, cloning, localization studies cited in review Der Urologe. Ausg. A Medium 8999630
2018 RNA aptamers (xPSM-A9 and xPSM-A10) that bind to the extracellular domain of PSMA inhibit its glutamate carboxypeptidase enzymatic activity and internalize into PSMA-expressing cancer cells, demonstrating that extracellular domain engagement is sufficient to inhibit catalytic function and trigger endocytosis. In vitro selection (SELEX) of 2'-fluorpyrimidine RNA aptamers, glutamate carboxypeptidase activity inhibition assay, internalization assays in PSMA-expressing prostate cancer cells American journal of clinical and experimental urology Medium 29666835
2016 FOLH1/GCPII enzymatic activity is elevated in colorectal tissues of mice with TNBS-induced colitis; 2-PMPA inhibits colonic GCPII activity by >90% and reduces disease activity when administered locally as an enema. Ex vivo enzymatic activity assays, TNBS-induced colitis mouse model, local enema delivery of 2-PMPA, macroscopic and microscopic disease scoring Journal of controlled release Medium 28159515
2016 MDM2 knockdown reduces PSMA expression and vice versa in metastatic breast cancer cells; siRNA-mediated PSMA knockdown decreases cell growth, adhesion, migration, and invasion, and alters MMP expression (decreasing MMP2, increasing MMP3/10/13), placing PSMA in a pathway regulating matrix metalloproteinase activity. siRNA knockdown, qPCR, western blotting, proliferation/adhesion/migration/invasion assays in MDA-MB-231 and ZR-75.1 cells Anticancer research Medium 26977010

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer research 723 10397265
2004 Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. Journal of cellular biochemistry 662 14755683
2016 PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 486 26985056
2016 Current use of PSMA-PET in prostate cancer management. Nature reviews. Urology 475 26902337
2015 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 422 26089548
1999 Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nature medicine 261 10581082
2014 Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer cell international 166 24645697
2001 Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. Mammalian genome : official journal of the International Mammalian Genome Society 142 11210180
2018 A Perspective on the Evolving Story of PSMA Biology, PSMA-Based Imaging, and Endoradiotherapeutic Strategies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 141 29674422
2018 Neuroendocrine differentiation of prostate cancer leads to PSMA suppression. Endocrine-related cancer 138 30400059
2017 Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 138 28775203
2019 PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy. Seminars in nuclear medicine 122 31227053
2021 Advances in PSMA-targeted therapy for prostate cancer. Prostate cancer and prostatic diseases 113 34050265
2013 PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials 103 23777916
2017 PSMA-11-Derived Dual-Labeled PSMA Inhibitors for Preoperative PET Imaging and Precise Fluorescence-Guided Surgery of Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 101 29191856
2004 Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histology and histopathology 94 15168332
2024 Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer. Nature reviews. Urology 90 38977769
2013 Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence. PLoS pathogens 89 23592990
2001 A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Genomics 89 11350116
1992 Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase). The Journal of comparative neurology 87 1545010
1998 Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase). The Journal of pharmacology and experimental therapeutics 79 9694964
2017 PSMA expression by microvasculature of thyroid tumors - Potential implications for PSMA theranostics. Scientific reports 73 28701709
2003 Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer research 73 12750292
2011 Construction of a DOPC/PSM/cholesterol phase diagram based on the fluorescence properties of trans-parinaric acid. Langmuir : the ACS journal of surfaces and colloids 71 21627141
2023 Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer. JCI insight 67 36821396
2018 Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clinical & experimental metastasis 67 29426963
2017 Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 66 28986509
2001 Design of NAALADase inhibitors: a novel neuroprotective strategy. Current medicinal chemistry 64 11375762
2001 Four PSM/SH2-B alternative splice variants and their differential roles in mitogenesis. The Journal of biological chemistry 63 11502739
2017 Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer. PloS one 62 29077706
2007 Arabidopsis GCP2 and GCP3 are part of a soluble gamma-tubulin complex and have nuclear envelope targeting domains. The Plant journal : for cell and molecular biology 60 17714428
2019 Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate cancer and prostatic diseases 55 31595044
2015 (R)-NODAGA-PSMA: A Versatile Precursor for Radiometal Labeling and Nuclear Imaging of PSMA-Positive Tumors. PloS one 54 26700033
2019 A Review of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in Renal Cell Carcinoma (RCC). Molecular imaging and biology 53 30617728
2009 Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism. Journal of neurochemistry 53 19895667
2023 PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials. The oncologist 50 36806966
2017 Metal-Based PSMA Radioligands. Molecules (Basel, Switzerland) 50 28338640
2020 Toward the Discovery and Development of PSMA Targeted Inhibitors for Nuclear Medicine Applications. Current radiopharmaceuticals 49 31362683
2001 PSMA specific antibodies and their diagnostic and therapeutic use. Expert opinion on investigational drugs 49 11227049
2017 Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy. Applied immunohistochemistry & molecular morphology : AIMM 43 26862945
2021 Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. International journal of molecular sciences 42 34299051
2003 Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney international 42 12753319
2014 Heterobivalent agents targeting PSMA and integrin-αvβ3. Bioconjugate chemistry 41 24410012
2016 PSM-Mec-A Virulence Determinant that Connects Transcriptional Regulation, Virulence, and Antibiotic Resistance in Staphylococci. Frontiers in microbiology 40 27597849
2021 PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga. Hepatology communications 39 34783177
2002 Morphine tolerance and reward but not expression of morphine dependence are inhibited by the selective glutamate carboxypeptidase II (GCP II, NAALADase) inhibitor, 2-PMPA. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39 12629525
2022 Hetero-bivalent agents targeting FAP and PSMA. European journal of nuclear medicine and molecular imaging 37 35965291
2016 FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities. JCI insight 37 27536732
2020 Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck. BMC cancer 36 32503460
2016 Small-molecule PSMA ligands. Current state, SAR and perspectives. Journal of drug targeting 36 26887438
2018 Expression of Prostate-Specific Membrane Antigen (PSMA) in Brain Glioma and its Correlation with Tumor Grade. Iranian journal of pathology 35 29731795
2016 Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment. Molecular cancer research : MCR 35 27458033
2019 Renal Cell Carcinoma: the Oncologist Asks, Can PSMA PET/CT Answer? Current urology reports 33 31605269
2022 Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC. Cancers 31 35406467
2020 Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors. Journal of medicinal chemistry 30 32852205
2015 Evaluation of a PSMA-targeted BNF nanoparticle construct. Nanoscale 30 25675333
2017 Comparison of PSMA-HBED and PSMA-I&T as diagnostic agents in prostate carcinoma. European journal of nuclear medicine and molecular imaging 28 28474140
2020 Acute Statin Treatment Improves Antibody Accumulation in EGFR- and PSMA-Expressing Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 27 32998959
2015 Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma. Journal of neuropathology and experimental neurology 27 26079448
2022 Radiosynthesis and Preclinical Evaluation of Bispecific PSMA/FAP Heterodimers for Tumor Imaging. Pharmaceuticals (Basel, Switzerland) 26 35337180
2022 Pharmacological Optimization of PSMA-Based Radioligand Therapy. Biomedicines 26 36551776
2019 68Ga-PSMA PET thyroid incidentalomas. Hormones (Athens, Greece) 26 30989578
2023 PSMA-targeted therapy for non-prostate cancers. Frontiers in oncology 25 37645427
2021 The VISION Forward: Recognition and Implication of PSMA-/18F-FDG+ mCRPC. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 25 34933889
2006 Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic strategy. Advances in experimental medicine and biology 25 16802724
2005 Correlation between PSMA and VEGF expression as markers for LNCaP tumor angiogenesis. Journal of biomedicine & biotechnology 25 16192687
2021 Ga-68 PSMA PET/CT in recurrent high-grade gliomas: evaluating PSMA expression in vivo. Neuroradiology 24 34648046
2003 Reduced isolation-induced aggressiveness in mice following NAALADase inhibition. Psychopharmacology 24 14634711
1999 Blockade of NAALADase: a novel neuroprotective strategy based on limiting glutamate and elevating NAAG. Annals of the New York Academy of Sciences 24 10668445
2020 Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions. Diagnostic pathology 21 32703222
2019 Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates. Bioorganic & medicinal chemistry letters 21 31248772
2008 Identification of presomitic mesoderm (PSM)-specific Mesp1 enhancer and generation of a PSM-specific Mesp1/Mesp2-null mouse using BAC-based rescue technology. Mechanisms of development 21 18328678
2023 The current status of prostate cancer treatment and PSMA theranostics. Therapeutic advances in medical oncology 20 37424944
2003 Expression pattern of mouse homolog of prostate-specific membrane antigen (FOLH1) in the transgenic adenocarcinoma of the mouse prostate model. The Prostate 20 12712410
2022 Relative Efficacy of 225Ac-PSMA-617 and 177Lu-PSMA-617 in Prostate Cancer Based on Subcellular Dosimetry. Molecular imaging and radionuclide therapy 19 35114745
2020 Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice. Scientific reports 19 33273603
2023 The Potential of PSMA as a Vascular Target in TNBC. Cells 18 36831218
2020 PSMA-PET and micro-ultrasound potential in the diagnostic pathway of prostate cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 18 32447644
2017 Local enema treatment to inhibit FOLH1/GCPII as a novel therapy for inflammatory bowel disease. Journal of controlled release : official journal of the Controlled Release Society 18 28159515
1996 [Significance of prostate-specific membrane antigen (PSMA). A neurocarboxypeptidase and membrane folate hydrolase]. Der Urologe. Ausg. A 18 8999630
2022 Lutetium-177-PSMA-617: A Vision of the Future. Cancer biology & therapy 17 35220877
2016 Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands. European journal of medicinal chemistry 16 27128184
2011 N-substituted glutamyl sulfonamides as inhibitors of glutamate carboxypeptidase II (GCP2). Chemical biology & drug design 16 21219587
2004 Patterns and clusters within the PSM column in TiBS, 1992-2004. Trends in biochemical sciences 16 15544947
2020 Mechanistic Insights for Optimizing PSMA Radioligand Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 15 32253231
2016 MADD-FOLH1 Polymorphisms and Their Haplotypes with Serum Lipid Levels and the Risk of Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population. Nutrients 15 27070640
2022 Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer. Geburtshilfe und Frauenheilkunde 14 35027860
2019 Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA. Bioorganic & medicinal chemistry letters 14 30904185
2008 Essential role of PSM/SH2-B variants in insulin receptor catalytic activation and the resulting cellular responses. Journal of cellular biochemistry 14 17615553
2018 Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey. American journal of clinical and experimental urology 13 29666835
2023 Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas. The British journal of radiology 12 36728839
2019 68Ga-RM2 PET in PSMA- positive and -negative prostate cancer patients. Nuklearmedizin. Nuclear medicine 12 31443113
2018 Sox7 negatively regulates prostate-specific membrane antigen (PSMA) expression through PSMA-enhancer. The Prostate 12 30488457
2016 MDM2 and PSMA Play Inhibitory Roles in Metastatic Breast Cancer Cells Through Regulation of Matrix Metalloproteinases. Anticancer research 12 26977010
2024 The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer. Cancers 11 38473301
2023 Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R. Cancers 11 37190273
2022 Dose response modelling of secretory cell loss in salivary glands using PSMA PET. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 11 36368471
2018 Association of FOLH1, DHFR, and MTHFR gene polymorphisms with susceptibility of Neural Tube Defects: A case control study from Eastern India. Birth defects research 11 30120883
2008 PSM/SH2B1 splice variants: critical role in src catalytic activation and the resulting STAT3s-mediated mitogenic response. Journal of cellular biochemistry 11 18247337
2007 Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks. European journal of pharmacology 11 18031726