Affinage

EMP1

Epithelial membrane protein 1 · UniProt P54849

Length
157 aa
Mass
17.6 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 19 extracted findings
Cross-family judge faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EMP1 (TMP/CL-20) is a tetraspan integral membrane glycoprotein of the PMP22 family that functions at epithelial cell junctions and as a regulator of epithelial proliferation, cell-state plasticity, and cancer progression (PMID:9126480, PMID:16036215). It localizes to intercellular borders and epithelial junctions, including bile duct epithelia and bile canaliculi, marking it as a junctional protein (PMID:16036215), and it is indispensable for tight junction assembly during airway morphogenesis downstream of SOS1/Ras/MEK/ERK signaling (PMID:25394671). EMP1 transcription is controlled at multiple levels: it is a direct c-Myc-Max target through a CACGTG E-box in its first intron, conferring tumorigenic activity when overexpressed (PMID:10207076); it is induced by ETV4 (PMID:34976153); and it is silenced epigenetically by SMYD3-mediated H4K20me3 deposition and post-transcriptionally by miR-95-3p and miR-34a (PMID:37386026, PMID:33714198, PMID:31450568). EMP1 exerts context-dependent effects on tumor behavior by modulating the PI3K/AKT/mTOR, RAS/RAF/MAPK, and NF-κB pathways: it activates PI3K-AKT and CD44-linked stemness in glioma (PMID:31111534), drives RAS/RAF/MAPK/c-JUN-dependent proliferation and EMT in ovarian cancer (PMID:32210572), and promotes IL-6 secretion via NF-κB to recruit cancer-associated fibroblasts in triple-negative breast cancer (PMID:40016223), while opposing AKT signaling and proliferation in gastric cancer (PMID:37386026). EMP1 loss confers ferroptosis resistance through PPARG-driven upregulation of pFAK and SLC7A11 in bladder cancer (PMID:35850179). In microsatellite-stable colorectal cancer, EMP1 marks a high-relapse residual tumor cell state whose genetic ablation prevents metastatic recurrence, and these EMP1+ cells convert to WNT-driven LGR5+ stem-like cells, including rapidly upon KRAS-G12D inhibition (PMID:36352230, PMID:41128661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Medium

    Established the molecular identity of EMP1 as a four-transmembrane PMP22-family membrane protein, providing the structural framework for all later functional work.

    Evidence cDNA cloning/sequencing, Northern analysis, and FISH mapping in human bronchial epithelial cells

    PMID:9126480

    Open questions at the time
    • No membrane topology confirmed experimentally
    • Function of the protein not addressed
    • Binding partners unknown
  2. 1998 Medium

    Confirmed EMP1 as part of a duplicated mammalian membrane glycoprotein family expressed in proliferative cells, hinting at a proliferation-linked role.

    Evidence cDNA isolation and chromosomal mapping by linkage and FISH in mouse

    PMID:9615230

    Open questions at the time
    • Correlation with proliferation not mechanistically tested
    • No functional assay
  3. 1999 High

    Answered how EMP1 connects to oncogenic transcription by showing it is a direct c-Myc target with intrinsic tumorigenic activity.

    Evidence Reporter assays, EMSA for c-Myc-Max binding to an intronic E-box, inducible MycER activation, and nude mouse xenografts

    PMID:10207076

    Open questions at the time
    • Downstream mechanism of tumorigenicity not defined
    • Did not address normal physiological role
  4. 2005 Medium

    Defined EMP1 as a bona fide junctional protein by localizing it to epithelial cell-cell borders and bile canaliculi.

    Evidence Immunofluorescence/IHC with anti-EMP1 antiserum and co-localization with dipeptidyl peptidase IV in liver tissue and a liver stem cell line

    PMID:16036215

    Open questions at the time
    • Functional role at junctions not tested
    • No interacting junctional proteins identified
  5. 2014 High

    Provided a physiological function by placing EMP1 downstream of SOS1/Ras/MEK/ERK as an essential factor for tight junction assembly.

    Evidence GEF RNAi screen, microarray identification of EMP1 as pathway target, and EMP1 knockdown with tight junction readouts in two human airway cell lines

    PMID:25394671

    Open questions at the time
    • Molecular mechanism by which EMP1 promotes junction assembly unknown
    • Direct junctional partners not identified
  6. 2019 Medium

    Showed EMP1 can act oncogenically through PI3K-AKT signaling and stemness, broadening its role beyond junction biology.

    Evidence EMP1 siRNA knockdown in glioma cells with proliferation/invasion assays and PI3K-AKT and CD44 readouts

    PMID:31111534

    Open questions at the time
    • No direct link between EMP1 and PI3K-AKT components
    • Gain-of-function not included
  7. 2020 Medium

    Extended EMP1 oncogenic signaling to the RAS/RAF/MAPK/c-JUN axis driving proliferation, invasion, and EMT.

    Evidence siRNA and overexpression in ovarian cancer cells with phenotypic assays and Western blot of pathway components

    PMID:32210572

    Open questions at the time
    • Pathway activation inferred from protein levels, not direct binding
    • Tissue specificity of the axis unclear
  8. 2022 High

    Identified EMP1 as a functional marker of high-relapse residual tumor cells whose elimination prevents metastatic recurrence.

    Evidence Single-cell transcriptomics, genetic ablation of EMP1-high cells, and in vivo tracking in a microsatellite-stable CRC mouse model

    PMID:36352230

    Open questions at the time
    • Whether EMP1 protein is causal or merely a marker not resolved
    • Mechanism of EMP1+ to LGR5+ transition not defined here
  9. 2023 Medium

    Revealed epigenetic control of EMP1 by SMYD3 and a tumor-suppressive output via AKT, illustrating its context-dependent role.

    Evidence ChIP for H4K20me3 at the EMP1 locus, SMYD3 knockdown, and EMP1 gain-of-function/rescue with p-Akt readout in gastric cancer cells

    PMID:37386026

    Open questions at the time
    • How EMP1 suppresses AKT mechanistically unknown
    • Reconciliation with oncogenic PI3K-AKT activation in other tissues unaddressed
  10. 2021 Medium

    Defined transcriptional and post-transcriptional regulators of EMP1 (ETV4, miR-95-3p, miR-34a) linking its expression to PI3K/AKT-driven phenotypes and drug resistance.

    Evidence Luciferase reporter and ChIP for ETV4, dual-luciferase miRNA-target validation, and rescue experiments with downstream pathway readouts in GBM and gastric cancer

    PMID:31450568 PMID:33714198 PMID:34976153

    Open questions at the time
    • Opposing directions of EMP1 effect across these studies not unified
    • Direct effectors downstream of EMP1 not isolated
  11. 2022 Medium

    Linked EMP1 loss to ferroptosis resistance and migration through a PPARG-pFAK-SLC7A11 program.

    Evidence EMP1 knockdown/overexpression in bladder cancer cells with ferroptosis and migration assays, PPARG ligand treatment, and FABP4 siRNA rescue

    PMID:35850179

    Open questions at the time
    • Mechanism by which EMP1 restrains PPARG unknown
    • Single cell-line context
  12. 2025 Medium

    Showed EMP1 shapes the tumor microenvironment by driving NF-κB-dependent IL-6 secretion and CAF infiltration.

    Evidence Co-culture, xenografts, loss/gain-of-function, RNA-seq, IL-6 ELISA, and NF-κB Western blot in TNBC

    PMID:40016223

    Open questions at the time
    • How a tetraspan membrane protein activates NF-κB not defined
    • Direct EMP1 signaling partners unidentified
  13. 2026 Medium

    Demonstrated that EMP1+ tumor cells undergo rapid KRAS-inhibition-driven conversion to LGR5+ stem-like cells via transcription factor rewiring, identifying a plasticity mechanism underlying relapse.

    Evidence Preclinical CRC mouse models, RAS(ON) inhibitor treatment, transcriptomic cell-state profiling, chromatin analysis, and genetic ablation of LGR5+ cells

    PMID:41128661

    Open questions at the time
    • Role of EMP1 protein itself in the conversion not isolated
    • Transcription factors driving the switch not fully enumerated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what direct molecular partners EMP1 engages at the membrane to transduce its signaling and junctional functions, and how the same protein produces opposing tumor-suppressive and oncogenic outputs across tissues.
  • No direct physical interactor or receptor identified
  • No structural model of the tetraspan protein in complex
  • Context-determinant of suppressor-vs-oncogene switch unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The Tmp gene (encoding EMP1) is a direct transcriptional target of the c-Myc oncoprotein. The c-Myc–Max protein complex binds to a CACGTG E-box element located in the first intron of Tmp, and an inducible MycER fusion protein activates the endogenous Tmp gene. Overexpression of Tmp in fibroblasts induces rapidly growing tumors in nude mice, indicating tumorigenic activity. Reporter gene assays with Tmp promoter/intron constructs, EMSA (c-Myc-Max binding to CACGTG element), inducible MycER system for endogenous gene activation, nude mouse xenograft tumorigenic assay Molecular and cellular biology High 10207076
1997 CL-20/EMP1 encodes an integral membrane protein of 157 amino acids with four hydrophobic transmembrane domains, placing it in the PMP22 gene family. The second hydrophobic domain (fourth exon) is highly conserved among CL-20, EMP-1, and PMP22, suggesting a functional role. EMP1 mRNA is abundant in squamous-differentiated bronchial epithelial cells and is repressed by retinoic acid. The human gene maps to chromosome 12p12. cDNA cloning and sequencing, Northern analysis, FISH chromosomal mapping, retinoic acid treatment of normal human bronchial epithelial cells Genomics Medium 9126480
1998 Chromosomal mapping identified Tmp (Emp1) as a member of a novel mammalian membrane glycoprotein family with four transmembrane domains related to Pmp22. Mouse Tmp was mapped to chromosome 6, and it was expressed in highly proliferative cell types. The gene family is proposed to have evolved through chromosomal duplications. cDNA isolation, chromosomal mapping by linkage analysis and fluorescence in situ hybridization Genomics Medium 9615230
2005 EMP1 (EMP-1) localizes to intercellular borders in a liver stem cell line (Lig-8) and to epithelial junctions (bile duct epithelia, oval cell ductules, bile canaliculi) in the liver harboring proliferating oval cells. Co-localization with dipeptidyl peptidase IV confirmed junctional localization at bile canaliculi, establishing EMP1 as a junctional protein. Immunofluorescence and immunohistochemistry with anti-EMP1 antiserum on cell monolayers and liver tissue sections; co-localization with dipeptidyl peptidase IV marker Biochemical and biophysical research communications Medium 16036215
2014 SOS1 acts through the Ras/MEK/ERK pathway to transcriptionally upregulate EMP1 in human bronchial epithelial cells (16HBE). EMP1 is indispensable for tight junction formation and function in 16HBE cells and in a human airway basal progenitor-like cell line (BCi-NS1.1); RNAi knockdown of EMP1 disrupts tight junction assembly during airway morphogenesis. RNAi screen for GEFs in 16HBE cells, global microarray analysis identifying EMP1 as SOS1/Ras/MEK/ERK transcriptional target, EMP1 knockdown with tight junction functional readouts in two human airway cell lines EMBO reports High 25394671
2017 EMP1 loss in bladder cancer cells promotes migration and confers resistance to ferroptosis/oxidative stress by increasing PPARG expression and its activation, leading to upregulation of pFAK(Y397) (promoting migration) and SLC7A11 (promoting anti-ferroptotic cell death). EMP1-deficient cells were sensitized to PPARG ligand; FABP4 knockdown mitigated this effect. EMP1 knockdown/overexpression in BCa cells, Western blot for PPARG/pFAK/SLC7A11, migration assays, ferroptosis/oxidative stress assays, PPARG ligand treatment, FABP4 siRNA rescue experiments Free radical biology & medicine Medium 35850179
2020 EMP1 overexpression in ovarian cancer cells promotes proliferation, invasion, and EMT by activating the RAS/RAF/MAPK/c-JUN signaling pathway, as shown by increased protein levels of these components after EMP1 overexpression and inhibition of these phenotypes by EMP1 siRNA. siRNA interference, colony formation, migration and invasion assays, Western blot for RAS/RAF/MAPK/c-JUN pathway components OncoTargets and therapy Medium 32210572
2019 EMP1 promotes glioma cell proliferation, migration, invasion, and stemness through activation of the PI3K-AKT signaling pathway and regulation of CD44 expression in glioma stem cells. Silencing EMP1 inhibited these processes by suppressing PI3K-AKT signaling. EMP1 siRNA knockdown in glioma cells, invasion/proliferation assays, Western blot for PI3K-AKT pathway, CD44 expression analysis in glioma stem cells Journal of cellular biochemistry Medium 31111534
2012 EMP1 overexpression in NSCLC cell line PC9 promotes proliferation and activates the PI3K/AKT signaling pathway; EMP1 promoted growth of PC9 xenografts in nude mice. Recombinant adenovirus overexpression of EMP1, Ki67 staining for proliferation, Western blot for PI3K/AKT pathway, subcutaneous xenograft tumor model Journal of Huazhong University of Science and Technology. Medical sciences Low 23271282
2013 EMP1 overexpression in prostate cancer PC-3 cells increases apoptosis and decreases migration and invasion, associated with higher caspase-9 and lower VEGFC protein expression. EMP1 overexpression in nasopharyngeal cancer CNE2 cells similarly increases apoptosis, decreases migration/invasion, elevates caspase-9, and reduces VEGFC. EMP1 overexpression in breast cancer MCF-7 cells shows the same pattern. Lentiviral EMP1 overexpression, MTT/migration/invasion assays, Western blot for caspase-9 and VEGFC, flow cytometry for apoptosis Tumour biology Low 24292952 24338711 24402572
2002 Overexpression of EMP1 in the esophageal cancer cell line EC9706 accelerated cell growth and was linked to induction of S-phase cell cycle arrest. Eukaryotic vector transfection, Western blot/RT-PCR confirmation, cell growth curve, FACS cell cycle analysis Ai zheng = Chinese journal of cancer Low 12451984
2022 EMP1-high (HRC) residual tumor cells are responsible for metastatic recurrence in colorectal cancer. Using Emp1 as a marker, genetic ablation of EMP1-high cells prevented metastatic recurrence in a mouse model of microsatellite-stable CRC after primary tumor surgery. These cells gave rise to LGR5+ stem-like tumor cells over time during metastatic outgrowth, and their micrometastases transitioned from T-cell infiltrated to progressively immune-excluded. Single-cell transcriptomics, mouse model of CRC with surgical resection, genetic cell ablation of EMP1-high cells, tumor cell tracking over time in vivo Nature High 36352230
2023 The histone methyltransferase SMYD3 epigenetically represses EMP1 expression in gastric cancer cells in an H4K20me3-dependent manner. ChIP assays showed SMYD3-mediated H4K20me3 deposition at the EMP1 locus. EMP1, in turn, inhibits GC cell proliferation and reduces p-Akt (S473) levels. ChIP assay for H4K20me3 at EMP1 locus, SMYD3 shRNA knockdown, EMP1 gain-of-function and rescue experiments, Western blot for p-Akt (S473) Cell death & disease Medium 37386026
2021 ETV4 binds to the EMP1 promoter and positively regulates EMP1 transcription. Knockdown of ETV4 reduced EMP1 expression, inhibited PI3K/AKT/mTOR pathway activity, and promoted autophagy-dependent apoptosis in GBM cells; overexpressing EMP1 partially reversed these effects. Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) for ETV4 at EMP1 promoter, ETV4 knockdown with EMP1 rescue overexpression, Western blot for PI3K/AKT/mTOR and autophagy/apoptosis markers, TUNEL assay Oncology letters Medium 34976153
2021 miR-95-3p promotes cisplatin resistance in gastric cancer by directly targeting EMP1 (confirmed by dual luciferase assay), suppressing EMP1 expression, and thereby activating PI3K/AKT signaling and promoting EMT and drug-resistance. EMP1 knockdown phenocopied miR-95-3p overexpression. Dual luciferase reporter assay to confirm miR-95-3p targeting of EMP1, qRT-PCR, Western blot, BrdU/MTT proliferation assays, transwell invasion/migration, in vivo tumorigenic experiments Aging Medium 33714198
2019 TFF3 signaling in Y79 retinoblastoma cells activates p53 and downstream miR-34a, which in turn inhibits EMP1 expression (as a predicted miR-34a target). EMP1 knockdown decreases viability and proliferation while increasing apoptosis (partially caspase-3/7 dependent) in Y79 cells; EMP1 overexpression produces the opposite effects. EMP1 overexpressing cells also show increased colony formation and larger CAM tumors. pG13-luciferase reporter for p53 activity, Western blot, WST-1 and BrdU assays, DAPI counts, caspase-3/7 assay, colony formation, soft agarose, in ovo CAM assay, EMP1 knockdown/overexpression International journal of molecular sciences Medium 31450568
2025 EMP1 expression in TNBC cells is required for cancer-associated fibroblast (CAF) infiltration in the tumor microenvironment. Mechanistically, EMP1 knockdown substantially decreased IL-6 secretion from TNBC cells through the NF-κB signaling pathway, reducing CAF proliferation and inhibiting TNBC progression and metastasis in vitro and in vivo. Cell co-culture assays, xenograft tumor experiments, EMP1 loss-of-function and gain-of-function, RNA sequencing, rescue assays, IL-6 ELISA, Western blot for NF-κB pathway Cell death & disease Medium 40016223
2020 EMP1 promotes osteosarcoma malignant progression by upregulating IRX2 and subsequently MMP9. Knockdown of EMP1 inhibited migration and invasion; overexpression of EMP1 increased IRX2 and MMP9 protein levels; rescue experiments confirmed IRX2 is involved in EMP1-regulated osteosarcoma progression. Transwell and wound healing migration/invasion assays, EMP1 knockdown/overexpression, Western blot for IRX2 and MMP9, rescue experiments with IRX2 Panminerva medica Low 32716150
2026 In metastatic colorectal cancer, KRAS-G12D inhibition converts EMP1+ tumor cells to a WNT-driven LGR5+ stem cell-like state through a shift in transcription factor usage with limited chromatin remodeling, occurring within hours of treatment. Genetic ablation of the LGR5+ population after forced conversion reduced metastatic burden and prolonged survival. Preclinical colorectal cancer mouse models, RMC-9945 RAS(ON) inhibitor treatment, transcriptomic cell-state profiling, genetic ablation of LGR5+ cells, chromatin remodeling analysis Cancer discovery Medium 41128661

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells. Nature 188 36352230
2018 Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site. European journal of medicinal chemistry 170 29649743
2012 Second-generation covalent TMP-tag for live cell imaging. Journal of the American Chemical Society 101 22873118
2009 An in vivo covalent TMP-tag based on proximity-induced reactivity. ACS chemical biology 94 19492849
1987 2,2,4-Trimethylpentane-induced nephrotoxicity. II. The reversible binding of a TMP metabolite to a renal protein fraction containing alpha 2u-globulin. Toxicology and applied pharmacology 94 2445051
1998 Identification of a 13 amino acid peptide mimetic of erythropoietin and description of amino acids critical for the mimetic activity of EMP1. Biochemistry 91 9521688
2001 X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution. Journal of molecular biology 88 11469859
2014 Tetramethylpyrazine (TMP) protects against sodium arsenite-induced nephrotoxicity by suppressing ROS production, mitochondrial dysfunction, pro-inflammatory signaling pathways and programed cell death. Archives of toxicology 80 24961358
2017 EMP1, EMP 2, and EMP3 as novel therapeutic targets in human cancer. Biochimica et biophysica acta. Reviews on cancer 76 28408326
2006 Structure and reaction pathway of TMP-Zincate: amido base or alkyl base? Journal of the American Chemical Society 72 16819866
2006 Biodegradation of the cyclic nitramine explosives RDX, HMX, and CL-20. Applied microbiology and biotechnology 71 17058075
2013 A fluorogenic TMP-tag for high signal-to-background intracellular live cell imaging. ACS chemical biology 69 23745575
2008 Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke. Bioorganic & medicinal chemistry 68 18790647
1987 2,2,4-Trimethylpentane-induced nephrotoxicity. I. Metabolic disposition of TMP in male and female Fischer 344 rats. Toxicology and applied pharmacology 66 2445050
2002 Hydrolysis of the 5'-p-nitrophenyl ester of TMP by the proofreading exonuclease (epsilon) subunit of Escherichia coli DNA polymerase III. Biochemistry 55 11955076
2010 Chiral preference of L-tryptophan derived metal-based antitumor agent of late 3d-metal ions (Co(II), Cu(II) and Zn(II)) in comparison to D- and DL-tryptophan analogues: their in vitro reactivity towards CT DNA, 5'-GMP and 5'-TMP. European journal of medicinal chemistry 52 20537435
2022 Loss of EMP1 promotes the metastasis of human bladder cancer cells by promoting migration and conferring resistance to ferroptosis through activation of PPAR gamma signaling. Free radical biology & medicine 50 35850179
2020 EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway. OncoTargets and therapy 47 32210572
2013 Tetramethylpyrazine (TMP) protects cerebral neurocytes and inhibits glioma by down regulating chemokine receptor CXCR4 expression. Cancer letters 45 23523616
2012 TMP prevents retinal neovascularization and imparts neuroprotection in an oxygen-induced retinopathy model. Investigative ophthalmology & visual science 45 22410554
1998 Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes encoding membrane proteins related to Pmp22. Genomics 45 9615230
2004 Extracellular matrix protein gene, EMP1, is required for appressorium formation and pathogenicity of the rice blast fungus, Magnaporthe grisea. Molecules and cells 44 15055545
2015 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells. Archives of toxicology 43 26404762
2005 Proteomic studies of Plasmodium knowlesi SICA variant antigens demonstrate their relationship with P. falciparum EMP1. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 43 16376842
2019 EMP1 regulates cell proliferation, migration, and stemness in gliomas through PI3K-AKT signaling and CD44. Journal of cellular biochemistry 40 31111534
2010 The expression of EMP1 is downregulated in oral squamous cell carcinoma and possibly associated with tumour metastasis. Journal of clinical pathology 40 20980531
2020 CircMACF1 Attenuates Acute Myocardial Infarction Through miR-500b-5p-EMP1 Axis. Journal of cardiovascular translational research 39 32162171
2002 Molecular cloning and purification of Ac-TMP, a developmentally regulated putative tissue inhibitor of metalloprotease released in relative abundance by adult Ancylostoma hookworms. The American journal of tropical medicine and hygiene 38 12139214
2014 A rapid and fluorogenic TMP-AcBOPDIPY probe for covalent labeling of proteins in live cells. Journal of the American Chemical Society 37 24598024
2013 EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction apoptosis and angiogenesis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 24292952
2015 Tetramethylpyrazine (TMP) exerts antitumor effects by inducing apoptosis and autophagy in hepatocellular carcinoma. International immunopharmacology 36 25841319
2009 The hookworm tissue inhibitor of metalloproteases (Ac-TMP-1) modifies dendritic cell function and induces generation of CD4 and CD8 suppressor T cells. PLoS neglected tropical diseases 35 19468296
1999 The tmp gene, encoding a membrane protein, is a c-Myc target with a tumorigenic activity. Molecular and cellular biology 35 10207076
2013 EMP1 regulates caspase-9 and VEGFC expression and suppresses prostate cancer cell proliferation and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 24338711
1999 Atovaquone suspension in HIV-infected volunteers: pharmacokinetics, pharmacodynamics, and TMP-SMX interaction study. Pharmacotherapy 32 10610011
2022 Third-Generation Covalent TMP-Tag for Fast Labeling and Multiplexed Imaging of Cellular Proteins. Angewandte Chemie (International ed. in English) 30 35816052
2009 Mutational, inhibitory and microcalorimetric analyses of Plasmodium falciparum TMP kinase. Implications for drug discovery. Parasitology 29 19126267
2012 EMP-1 promotes tumorigenesis of NSCLC through PI3K/AKT pathway. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 28 23271282
2010 Design and synthesis of heterobimetallic topoisomerase I and II inhibitor complexes: in vitro DNA binding, interaction with 5'-GMP and 5'-TMP and cleavage studies. Journal of photochemistry and photobiology. B, Biology 28 20638859
2013 Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia in nasal polyps. Histopathology 27 24033346
2008 A new interpretation of the reaction pathway of deprotonative metalation with TMP-Zn-ate/TMEDA Complex [TMEDA.Na(micro-tBu)(micro-TMP)Zn(tBu)]. The Journal of organic chemistry 27 18173282
2021 MicroRNA-95-3p serves as a contributor to cisplatin resistance in human gastric cancer cells by targeting EMP1/PI3K/AKT signaling. Aging 26 33714198
2014 EMP1, a member of a new family of antiproliferative genes in breast carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 24402572
2014 SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. EMBO reports 26 25394671
2005 EMP-1 is a junctional protein in a liver stem cell line and in the liver. Biochemical and biophysical research communications 25 16036215
2004 Initial reaction(s) in biotransformation of CL-20 is catalyzed by salicylate 1-monooxygenase from Pseudomonas sp. strain ATCC 29352. Applied and environmental microbiology 25 15240281
2003 Biotransformation of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) by denitrifying Pseudomonas sp. strain FA1. Applied and environmental microbiology 25 12957905
1997 cDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family. Genomics 25 9126480
2020 Role of Plasmodium falciparum Protein GEXP07 in Maurer's Cleft Morphology, Knob Architecture, and P. falciparum EMP1 Trafficking. mBio 24 32184257
2004 Preliminary ecotoxicological characterization of a new energetic substance, CL-20. Chemosphere 24 15234161
2009 Simultaneous quantification of 5-FU, 5-FUrd, 5-FdUrd, 5-FdUMP, dUMP and TMP in cultured cell models by LC-MS/MS. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 21 19620028
2004 Nitroreductase catalyzed biotransformation of CL-20. Biochemical and biophysical research communications 20 15313201
2019 Tetramethylpyrazine (TMP) protects rats against acute pancreatitis through NF-κB pathway. Bioengineered 19 31034353
2019 Decomposition Mechanism of Hexanitrohexaazaisowurtzitane (CL-20) by Coupled Computational and Experimental Study. The journal of physical chemistry. A 18 30995040
2018 Effect of density on the thermal decomposition mechanism of ε-CL-20: a ReaxFF reactive molecular dynamics simulation study. Physical chemistry chemical physics : PCCP 18 30116820
2000 Expression of Fas antigen and apoptosis caused by 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on carcinoma cells: implication for photodynamic therapy. Toxicology 18 10967404
2023 SMYD3 drives the proliferation in gastric cancer cells via reducing EMP1 expression in an H4K20me3-dependent manner. Cell death & disease 17 37386026
2020 Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection. HIV medicine 17 33277811
2018 Tetramethylpyrazine (TMP) ameliorates corneal neovascularization via regulating cell infiltration into cornea after alkali burn. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 30551354
2015 Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis. PloS one 17 26275042
2012 New [Ru(5,6-dmp/3,4,7,8-tmp)₂(diimine)]²⁺ complexes: non-covalent DNA and protein binding, anticancer activity and fluorescent probes for nuclear and protein components. Journal of inorganic biochemistry 17 23022692
2001 Molecular cloning of a cDNA for rat TM4SF4, a homolog of human il-TMP (TM4SF4), and enhanced expression of the corresponding gene in regenerating rat liver(1). Biochimica et biophysica acta 17 11267677
1999 The highly similar TMP kinases of Yersinia pestis and Escherichia coli differ markedly in their AZTMP phosphorylating activity. European journal of biochemistry 17 10491164
2019 p53, miR-34a and EMP1-Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells. International journal of molecular sciences 16 31450568
2010 Physiological stress and innate immune response in gilthead sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax) exposed to combination of trimethoprim and sulfamethoxazole (TMP-SMX). Fish physiology and biochemistry 16 20924669
2022 Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer's clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1. PLoS pathogens 15 35930605
2021 Knockdown of ETV4 promotes autophagy-dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1. Oncology letters 14 34976153
2005 Biotransformation of CL-20 by a dehydrogenase enzyme from Clostridium sp. EDB2. Applied microbiology and biotechnology 14 15841370
1997 Purification and characterization of polyamine aminotransferase of Arthrobacter sp. TMP-1. Journal of biochemistry 14 9348081
2021 Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. Cancers 13 35008207
2009 Phosphorylation of dGMP analogs by vaccinia virus TMP kinase and human GMP kinase. Biochemical and biophysical research communications 13 19631609
2002 Severe thrombocytopenia possibly associated with TMP/SMX therapy. The Annals of pharmacotherapy 13 11816265
2023 Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro. Molecules (Basel, Switzerland) 12 36770940
2021 Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy. Antioxidants (Basel, Switzerland) 12 33799587
2008 Molecular cloning and characterization of Ac-TMP-2, a tissue inhibitor of metalloproteinase secreted by adult Ancylostoma caninum. Molecular and biochemical parasitology 12 18804124
2020 Circ100284 promotes invasion and migration of osteosarcoma cells by down-regulating PTEN and EMP1. European review for medical and pharmacological sciences 10 32633341
2015 Laccase-Catalyzed Surface Modification of Thermo-Mechanical Pulp (TMP) for the Production of Wood Fiber Insulation Boards Using Industrial Process Water. PloS one 10 26046652
2015 Ceramide and N,N,N-Trimethylphytosphingosine-Iodide (TMP-I)-Based Lipid Nanoparticles for Cancer Therapy. Pharmaceutical research 10 26337769
2014 Heart mitochondrial TTP synthesis and the compartmentalization of TMP. The Journal of biological chemistry 10 25505243
2006 Biodegradation kinetics of the nitramine explosive CL-20 in soil and microbial cultures. Biodegradation 10 17091356
2025 Tumor cell-derived EMP1 is essential for cancer-associated fibroblast infiltration in tumor microenvironment of triple-negative breast cancer. Cell death & disease 9 40016223
2024 Determining the mechanical and decomposition properties of high energetic materials (α-RDX, β-HMX, and ε-CL-20) using a neural network potential. Physical chemistry chemical physics : PCCP 9 38477375
2021 Theoretical prediction of the trigger linkage, cage strain, and explosive sensitivity of CL-20 in the external electric fields. Journal of molecular modeling 9 33598779
2021 Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels. ACS omega 9 34151118
2012 In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine-iodide (TMP) in liposomes for the treatment of angiogenesis and metastasis. International journal of pharmaceutics 9 22643227
2007 Hydrolysis of the 5'-p-nitrophenyl ester of TMP by oligoribonucleases (ORN) from Escherichia coli, Mycobacterium smegmatis, and human. Protein expression and purification 9 18023590
2005 Prediction of CL-20 chemical degradation pathways, theoretical and experimental evidence for dependence on competing modes of reaction. SAR and QSAR in environmental research 9 16272046
1994 Effects of dimethyl methylphosphonate (DMMP) and trimethylphosphate (TMP) on spermatogenesis of rat testis. Yonsei medical journal 9 8091797
2025 N-butylphthalide (NBP) and ligustrazine (TMP) triazole hybrids target the KEAP1-NRF2 pathway to inhibit ferroptosis and exert brain neuroprotectivity. Redox biology 8 40850191
2024 Study of the Photophysical Properties and the DNA Binding of Enantiopure [Cr(TMP)2(dppn)]3+ Complex. Inorganic chemistry 8 39626123
2020 Prophylactic antibiotic treatment with TMP-SMX decreased the incidence of interstitial pneumonia in patients with B-cell lymphoma on chemotherapy. BMC cancer 7 32770971
2002 [Effect of EMP-1 gene on human esophageal cancer cell line]. Ai zheng = Aizheng = Chinese journal of cancer 7 12451984
1989 TMP-reactive autoantibodies in human SLE sera demonstrate thymine-dependent oligonucleotide specificity. Biochemical and biophysical research communications 7 2471526
2021 Antibody- Based Immunotherapy Combined With Antimycotic Drug TMP- SMX to Treat Infection With Paracoccidioides brasiliensis. Frontiers in immunology 6 34737741
2020 EMP1 promotes the malignant progression of osteosarcoma through the IRX2/MMP9 axis. Panminerva medica 6 32716150
2020 Expression of EMP1, EMP2, and EMP3 in breast phyllodes tumors. PloS one 6 32857809
2020 Regional Differences in Penetration of the Protein Stabilizer Trimethoprim (TMP) in the Rat Central Nervous System. Frontiers in molecular neuroscience 6 33013318
2014 The crystal structure and morphology of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) p-xylene solvate: a joint experimental and simulation study. Molecules (Basel, Switzerland) 6 25401400
1975 Mitochondrial and cellular inhibition by the folate analogue pyrimethamine in Saccharomyces cerevisiae: reversal of cellular effects by TMP. Biochimica et biophysica acta 6 1092364
2026 A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer. Cancer discovery 5 41128661

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