Affinage

TACSTD2

Tumor-associated calcium signal transducer 2 · UniProt P09758

Length
323 aa
Mass
35.7 kDa
Annotated
2026-06-10
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TACSTD2 (TROP2) is a type I transmembrane glycoprotein that functions both as an epithelial cell-surface signal transducer and as a regulator of intercellular junction integrity, with prominent roles in carcinoma proliferation, survival, and metastasis (PMID:20858281, PMID:35730316). At the membrane it physically partners with tight-junction proteins claudin-1 and occludin and controls their localization and phosphorylation, and acts redundantly with EpCAM to stabilize claudin-7 at cell membranes during epithelial development, such that loss of TACSTD2 disrupts barrier function (PMID:29538454, PMID:32326212, PMID:35730316). Its activity is gated by sequential proteolysis: ADAM10 cleaves TROP2 within the first thyroglobulin-domain loop between R87 and T88 to drive metastatic dissemination, matriptase (restrained by the HAI-1 inhibitor) cleaves it in keratinocytes, and Src-induced cyclin D1 amplifies γ-secretase/TACE-mediated release of a TROP2 intracellular domain that accumulates in the nucleus to promote cancer stem-cell self-renewal (PMID:33839455, PMID:32326212, PMID:27634768). The cytoplasmic tail is phosphorylated on Ser303 by protein kinase C, and TROP2 raises intracellular calcium and signals through ERK MAPK, PI3K/AKT, and JAK2/STAT3 cascades to upregulate cyclins D1/E, suppress p27 and p16, and drive cell-cycle progression, invasion, and apoptosis resistance (PMID:7635574, PMID:20858281, PMID:30431125, PMID:29845216, PMID:32768481). TROP2 also complexes with β-catenin to block its proteasomal degradation, forming a positive feedback loop that sustains TROP2 transcription and EMT, and engages DSG2 to remodel desmosomes via EGFR/AKT signaling (PMID:37271476, PMID:35392784). TROP2 abundance is set by miR-125b-1 silencing, TFEB-driven transcription through a promoter E-box, and METTL3/METTL1 dual m6A/m7G RNA modification of its mRNA and tRNAs (PMID:23416980, PMID:35882754, PMID:37268280). Mutations in TACSTD2 that mislocalize the protein and abolish epithelial barrier function underlie gelatinous drop-like corneal dystrophy (PMID:15295654, PMID:23818740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Established that the TROP2 cytoplasmic tail is a substrate for intracellular signaling kinases, providing the first evidence that this surface glycoprotein transduces signals rather than acting purely structurally.

    Evidence In vitro PKC/PKA kinase assays with phosphopeptide mapping and in vivo 32P-labeling in ME180 cells

    PMID:7635574

    Open questions at the time
    • Downstream consequences of Ser303 phosphorylation not defined
    • No link to a specific signaling cascade established at this stage
  2. 2004 Medium

    Linked TACSTD2 to corneal dystrophy mechanistically by showing a disease mutation mislocalizes the protein away from cell-cell borders, implicating the transmembrane/cytoplasmic domain in proper membrane targeting.

    Evidence Immunofluorescence of wild-type vs C108R-mutant M1S1 in transfected CHO cells

    PMID:15295654

    Open questions at the time
    • Single ectopic expression system
    • Functional consequence for junctions not measured in this study
  3. 2010 Medium

    Defined the first concrete pro-tumorigenic signaling output of TROP2 by placing it upstream of ERK-driven cell-cycle progression.

    Evidence Gain/loss-of-function in pancreatic cancer cell lines with phospho-ERK/cyclin western blots and in vivo metastasis models

    PMID:20858281

    Open questions at the time
    • Mechanism connecting surface TROP2 to ERK activation unresolved
    • Single lab
  4. 2013 Medium

    Identified an upstream regulatory layer controlling TROP2 levels, showing miR-125b-1 loss derepresses TACSTD2 to drive MAPK dysfunction in HNSCC.

    Evidence miRNA profiling, luciferase reporter validation, and methylation analysis in cell lines and clinical samples

    PMID:23416980

    Open questions at the time
    • Other regulators of TACSTD2 expression not addressed
    • Single lab
  5. 2014 Medium

    Connected TROP2 to chemoresistance by showing it sustains TAp63-dependent apoptotic gene programs, framing TROP2 loss as a route to apoptosis evasion.

    Evidence siRNA knockdown in SCC lines with drug-induced apoptosis assays and TAp63 western blots

    PMID:24651436

    Open questions at the time
    • Direct molecular link between TROP2 and TAp63 not defined
    • Single lab
  6. 2016 Medium

    Resolved how oncogenic Src triggers TROP2 intracellular-domain signaling, identifying cyclin D1 as the transducer that promotes γ-secretase cleavage and nuclear ICD accumulation driving stem-cell self-renewal.

    Evidence v-Src transformation of prostate epithelial cells, prostatosphere assays, cyclin D1 epistasis, and ICD immunofluorescence

    PMID:27634768

    Open questions at the time
    • Nuclear targets of the TROP2 ICD not identified
    • Single lab
  7. 2018 Medium

    Demonstrated TROP2 governs tight-junction protein localization, showing it controls CLDN1/OCLN membrane distribution via phosphorylation and is required for HCV entry.

    Evidence siRNA silencing in hepatoma lines and primary hepatocytes with CLDN1/OCLN immunofluorescence and HCV infection assays

    PMID:29538454

    Open questions at the time
    • Kinase responsible for claudin/occludin phosphorylation not identified
    • Single lab
  8. 2018 Medium

    Extended TROP2 signaling to the JAK2/STAT3 axis through pharmacological and cytokine rescue epistasis in glioblastoma.

    Evidence Knockdown/overexpression with WP1066 inhibition and IL-6 rescue, phospho-JAK2/STAT3 western blots

    PMID:30431125

    Open questions at the time
    • Direct biochemical coupling of TROP2 to JAK2 unresolved
    • Single lab
  9. 2018 Low

    Associated TROP2 with PI3K/AKT activation in osteosarcoma proliferation and migration.

    Evidence Overexpression/knockdown in osteosarcoma lines with PI3K/AKT western blots and proliferation/migration assays

    PMID:29845216

    Open questions at the time
    • No upstream/downstream pathway validation beyond correlation
    • Single lab, single method set
  10. 2020 High

    Established matriptase as a TROP2 protease and positioned TROP2 with EpCAM as redundant HAI/matriptase-regulated stabilizers of claudins.

    Evidence In vitro reconstitution with purified proteins, 293T co-transfection with active-site/mutant controls, and HAI-1 siRNA epistasis in keratinocytes

    PMID:32326212

    Open questions at the time
    • Physiological setting of matriptase cleavage in vivo not established
    • Cleavage site within TROP2 not mapped here
  11. 2020 Low

    Linked TROP2-driven calcium release to AMPK-dependent p16 suppression and S-phase entry in OSCC.

    Evidence Calcium release assays, cell cycle analysis, P16 rescue, and AMPK western blots in OSCC lines

    PMID:32768481

    Open questions at the time
    • P16 overexpression could not rescue TROP2 effects, weakening the causal chain
    • AMPK-P16 mechanism shallow
    • Single lab
  12. 2021 High

    Identified the principal activating protease and cleavage site, showing ADAM10 cuts TROP2 between R87-T88 and that an uncleavable mutant abolishes metastatic dissemination.

    Evidence Edman degradation site mapping, Co-IP+MS, ADAM10 inhibitor/siRNA/shRNA, R87A-T88A mutagenesis, and xenograft metastasis model

    PMID:33839455

    Open questions at the time
    • Signaling events downstream of cleavage incompletely defined
    • Single lab
  13. 2022 High

    Provided in vivo genetic confirmation that TROP2 and EpCAM are functionally redundant in stabilizing claudin-7 and supporting epithelial development.

    Evidence EPCAM/TROP2 single and double knockout mouse models with claudin-7 localization analysis across tissues

    PMID:35730316

    Open questions at the time
    • Molecular mechanism of claudin-7 stabilization not resolved
    • Tissue-specific contributions not fully dissected
  14. 2022 Medium

    Identified DSG2 as a TROP2 physical partner and a route by which TROP2 destabilizes desmosomes to drive invasion via EGFR/AKT signaling.

    Evidence Co-IP+MS, gain/loss-of-function, electron microscopy of desmosomes, and pathway western blots in gastric cancer cells

    PMID:35392784

    Open questions at the time
    • Interaction interface not mapped
    • Single lab
  15. 2022 Medium

    Defined TFEB as a transcriptional activator of TACSTD2, showing tamoxifen-induced active TFEB drives Trop2 expression through a promoter E-box.

    Evidence TFEB knockdown, Trop2 promoter E-box luciferase reporter, and phospho-TFEB western blots in breast cancer cells

    PMID:35882754

    Open questions at the time
    • Broader signaling context of TFEB-TROP2 axis not defined
    • Single lab
  16. 2022 Medium

    Revealed post-transcriptional control of TROP2 protein output through dual m6A/m7G RNA modifications.

    Evidence METTL3/METTL1 CRISPR knockout, m6A/m7G assays, RNA-IP, and TROP2 overexpression rescue in bladder cancer

    PMID:37268280

    Open questions at the time
    • Relative contribution of m6A vs m7G to TROP2 levels not quantified
    • Single lab
  17. 2023 Medium

    Uncovered a TROP2/β-catenin positive feedback loop that stabilizes β-catenin and sustains TROP2 transcription to drive EMT and metastasis.

    Evidence Co-IP+MS, CETSA and Lys307/Glu310 mutagenesis with the inhibitor Bruceine D, and orthotopic metastasis model

    PMID:37271476

    Open questions at the time
    • Mechanism by which TROP2 blocks β-catenin ubiquitination not detailed
    • Single lab
  18. 2023 Low

    Associated TACSTD2 with platinum resistance in ovarian cancer via the Rap1/PI3K/AKT pathway.

    Evidence Single-cell RNA-seq, spatial transcriptomics, and pathway analysis with functional analysis in cell lines

    PMID:38817863

    Open questions at the time
    • Pathway placement rests largely on transcriptomics
    • Limited direct functional validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple TROP2 proteolytic events, junctional interactions, and intracellular signaling cascades are integrated into a single coherent regulatory program — and which kinase mediates TROP2-dependent claudin/occludin phosphorylation — remains unresolved.
  • No unified model linking ICD nuclear signaling to surface junction regulation
  • Kinase for claudin/occludin phosphorylation unidentified
  • Structural basis of partner interactions not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2
Pathway
R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2
Partners
ADAM10CLDN1CLDN7CTNNB1DSG2EPCAMMST1ROCLN

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TACSTD2/EGP-1 is phosphorylated in vivo on serine 303 in its cytoplasmic domain by protein kinase C (PKC); metabolic 32P-labeling and immunoprecipitation confirmed phosphorylation on serine, in vitro kinase assays identified PKC (not PKA) as the responsible kinase, and phosphopeptide mapping pinpointed serine 303. Phorbol ester treatment of ME180 cells increased EGP-1 phosphorylation, implicating PKC-mediated phosphorylation in signal transduction. Metabolic 32P-labeling, immunoprecipitation, in vitro PKC/PKA kinase assays, phosphoamino acid analysis, phosphopeptide mapping International journal of cancer High 7635574
2010 Trop2 expression activates the ERK MAPK pathway, increasing phospho-ERK1/2 levels, upregulating cyclin D1 and cyclin E, and downregulating p27, thereby promoting cell cycle progression, proliferation, foci formation, anchorage-independent growth, and metastasis in pancreatic cancer models. Overexpression/knockdown in murine and human cancer cell lines, western blotting for phospho-ERK1/2 and cell cycle proteins, subcutaneous and orthotopic tumor models, liver metastasis assays Molecular cancer Medium 20858281
2013 miR-125b-1 directly targets and suppresses TACSTD2 expression; loss of miR-125b-1 (associated with promoter hypermethylation in HNSCC) leads to TACSTD2 upregulation, which drives MAPK pathway dysfunction, contributing to head and neck squamous cell carcinoma pathogenesis. miRNA profiling, luciferase reporter validation, methylation analysis, TACSTD2 mRNA/protein measurement in cell lines and clinical samples Oncogene Medium 23416980
2014 Loss of TACSTD2 in squamous cell carcinoma (SCC) attenuates chemotherapeutic agent-induced apoptosis by reducing TAp63-dependent apoptotic gene expression; TACSTD2 knockdown significantly inhibited drug-induced apoptosis, and TACSTD2 was found to regulate apoptotic gene expression through TAp63. Immunohistochemistry of SCC tissues, siRNA knockdown of TACSTD2 in cell lines, apoptosis assays with chemotherapeutic reagents, western blot for TAp63 and apoptotic genes Cell death & disease Medium 24651436
2016 v-Src induces nuclear accumulation of the Trop2 intracellular domain (Trop2 ICD) via cyclin D1; cyclin D1 upregulates components of the Trop2 proteolytic activation complex (PS2, TACE/ADAM17) and represses the inhibitory component Numb, thereby enhancing γ-secretase-mediated cleavage of Trop2 and release of Trop2 ICD, which promotes prostate cancer stem cell self-renewal. v-Src transformation of primary murine prostate epithelial cells, prostatosphere formation assays, western blotting for PS2/TACE/Numb, immunofluorescence for nuclear Trop2 ICD, cyclin D1 overexpression/knockdown, patient tissue analysis Cancer research Medium 27634768
2018 TACSTD2/TROP2 interacts with CLDN1 (claudin-1) and OCLN (occludin) and regulates their cellular localization via phosphorylation; TACSTD2 silencing disrupts the linear membrane distribution of CLDN1 and OCLN in hepatoma cells and primary human hepatocytes, and dramatically inhibits HCV entry at the viral entry step. siRNA silencing of TACSTD2 in hepatoma cell lines and primary human hepatocytes, immunofluorescence for CLDN1/OCLN localization, phosphorylation analysis, HCV infection assays across genotypes PLoS pathogens Medium 29538454
2018 TROP2 promotes glioblastoma cell proliferation and metastasis by activating the JAK2/STAT3 signaling pathway; knockdown of TROP2 reduced JAK2 and STAT3 phosphorylation and decreased STAT3 target gene transcription, while JAK2/STAT3 inhibitor WP1066 negated TROP2 overexpression effects, and exogenous IL-6 rescued JAK2/STAT3 phosphorylation in TROP2-silenced cells. siRNA knockdown, overexpression, MTT/BrdU proliferation assays, Transwell migration, western blot for phospho-JAK2/STAT3, pharmacological inhibition with WP1066, IL-6 rescue experiment Oncology reports Medium 30431125
2018 TROP2 promotes osteosarcoma cell proliferation and migration via activation of the PI3K/AKT signaling pathway; overexpression of TROP2 significantly activated PI3K/AKT, while knockdown decreased cell growth and migration. Overexpression and knockdown in osteosarcoma cell lines, proliferation and migration assays, western blot for PI3K/AKT pathway components Molecular medicine reports Low 29845216
2020 Matriptase cleaves TROP2 in vitro when purified recombinant proteins are mixed, and TROP2 is cleaved in 293T cells upon co-transfection with matriptase but not with protease-disabled matriptase or the G827R ichthyosis mutant; in keratinocytes (HaCaT cells), siRNA knockdown of HAI-1 (but not HAI-2 alone) promotes endogenous TROP2 cleavage, and combined EpCAM+TROP2 knockdown markedly reduces claudin-1 and claudin-7 levels (partly reversed by chloroquine), establishing TROP2 and EpCAM as redundant regulators of claudin stability downstream of HAI/matriptase. In vitro reconstitution with purified proteins, co-transfection of 293T cells, siRNA knockdown in HaCaT keratinocytes, western blotting for cleaved TROP2/EpCAM fragments, claudin levels, lysosomal inhibitor (chloroquine) treatment Cells High 32326212
2020 Trop2 promotes intracellular calcium ion release in OSCC cells, drives cell cycle progression to S phase, and inhibits P16 expression through the AMPK pathway; Trop2-mediated Ca2+ release was mechanistically linked to AMPK-dependent suppression of P16. Calcium ion release assays, cell cycle analysis, P16 overexpression rescue, western blot for AMPK pathway, knockdown/overexpression in OSCC cell lines International journal of biological macromolecules Low 32768481
2021 Trop-2 undergoes proteolytic cleavage in the first thyroglobulin domain loop between residues R87 and T88 by ADAM10; coimmunoprecipitation and mass spectrometry revealed physical interaction of ADAM10 with Trop-2; ADAM10 inhibitors, siRNAs, and shRNAs abolished Trop-2 processing; the R87A-T88A mutant abolished xenograft metastatic dissemination, and the cleavage activates cancer growth and metastasis. Antibody targeting and N-terminal Edman degradation (cleavage site identification), molecular modeling, coimmunoprecipitation + mass spectrometry, immunofluorescence/confocal time-lapse, ADAM10 inhibitors, siRNA/shRNA knockdown, site-directed mutagenesis (R87A-T88A), xenograft metastasis model Neoplasia (New York, N.Y.) High 33839455
2022 EPCAM and TROP2 share redundant roles in stabilizing claudin-7 at cell membranes and supporting epithelial development; TROP2 deficiency in mice compounded EPCAM-deficiency phenotypes (reduced embryonic viability, shortened postnatal lifespan, loss of claudin-7 membrane localization), and TROP2 could compensate for EPCAM loss in claudin-7 stabilization in tissues co-expressing both proteins. EPCAM and TROP2 knockout mouse models, histology/immunofluorescence, claudin-7 protein localization and expression analysis in multiple tissues Biology open High 35730316
2022 TROP2 translation is enhanced by dual RNA modifications: METTL3-mediated m6A methylation of TROP2 mRNA promotes its translation, and METTL1-mediated m7G modification of specific tRNAs further enhances TROP2 protein production; METTL3/METTL1 double knockout inhibited bladder cancer proliferation/invasion, and TROP2 overexpression partially rescued this phenotype. m6A/m7G methylation assays, METTL3/METTL1 knockout (CRISPR), TROP2 overexpression rescue, in vitro and in vivo proliferation/invasion assays, RNA immunoprecipitation Cancer letters Medium 37268280
2023 Trop2 promotes breast cancer metastasis through a Trop2/β-catenin positive feedback loop; Trop2 physically complexes with β-catenin (identified by immunoprecipitation and mass spectrometry), preventing β-catenin ubiquitin-proteasome degradation and enabling nuclear translocation to transcribe Trop2. Bruceine D binds Trop2 at Lys307 and Glu310 (validated by cellular thermal shift assay and point mutation analyses), disrupts the complex, destabilizes β-catenin, and inhibits EMT and ECM remodeling. Cell membrane chromatography screening, cellular thermal shift assay, point mutation analysis (Lys307/Glu310), immunoprecipitation + mass spectrometry, immunofluorescence, western blot, orthotopic metastasis model Journal of advanced research Medium 37271476
2022 TROP2 physically interacts with DSG2 (desmoglein-2) in gastric cancer cells (identified by co-immunoprecipitation and mass spectrometry); TROP2 overexpression reduces DSG2 levels and desmosome assembly, increasing cell invasion and migration via EGFR/AKT and DSG2/plakoglobin/β-catenin pathways. Co-immunoprecipitation, mass spectrometry, TROP2 overexpression and knockdown, electron microscopy for desmosome assembly, western blot for EGFR/AKT and DSG2/PG/β-catenin pathway proteins, adhesion and invasion assays Current cancer drug targets Medium 35392784
2004 The TACSTD2/M1S1 C108R missense mutation causes the protein to be distributed diffusely in the cytoplasm rather than accumulating at cell-to-cell adhesion borders (as normal TACSTD2 does), demonstrating that the transmembrane/cytoplasmic domain is required for proper membrane localization. Expression vectors for normal and C108R-mutant M1S1 transfected into CHO cells, immunofluorescence localization Japanese journal of ophthalmology Medium 15295654
2012 A GDLD patient-derived conjunctival epithelial cell line lacking functional TACSTD2 has significantly reduced tight junction protein expression and markedly lower transepithelial resistance compared to normal conjunctival epithelial cells, establishing TACSTD2 as necessary for epithelial barrier function. Immortalized patient cell line (lentiviral SV40T/hTERT), protein expression analysis of tight junction proteins, transepithelial resistance (TER) measurements Transactions of the American Ophthalmological Society Medium 23818740
2023 TACSTD2 promotes platinum resistance in high-grade serous ovarian cancer via the Rap1/PI3K/AKT pathway; RNA-seq analysis of a TACSTD2-representative cisplatin-resistant epithelial subcluster (E0) identified this pathway as the mechanistic basis. Single-cell RNA sequencing, spatial transcriptomics, RNA-seq pathway analysis, TACSTD2 functional analysis in cell lines Journal of Cancer Low 38817863
2023 TACSTD2 expression in breast cancer cells is regulated by transcription factor EB (TFEB): tamoxifen induces TFEB dephosphorylation (active form), and active TFEB drives TACSTD2 transcription through a tandem E-box motif in the Trop2 promoter; TFEB depletion prevented tamoxifen-induced Trop2 upregulation. TFEB knockdown, luciferase reporter assay with Trop2 promoter E-box motif, western blotting for phospho-TFEB, kinase inhibitor panel, RT-qPCR/western blot for Trop2 Breast cancer (Tokyo, Japan) Medium 35882754

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 405 26101915
2015 Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes & cancer 337 26000093
2021 Datopotamab Deruxtecan, a Novel TROP2-directed Antibody-drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells. Molecular cancer therapeutics 269 34413126
2018 The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 263 29989029
2011 Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 213 21551320
2010 Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Molecular cancer 189 20858281
2009 Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochimica et biophysica acta 158 19683559
2019 Targeting Trop-2 in solid tumors: future prospects. OncoTargets and therapy 143 30881031
2019 Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan. mAbs 132 31208270
2020 Trop2: Jack of All Trades, Master of None. Cancers 116 33187148
2022 Antibody-drug conjugates targeting TROP-2: Clinical development in metastatic breast cancer. Breast (Edinburgh, Scotland) 114 36302269
2022 Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. Pharmacology & therapeutics 105 36208791
2015 Trop2: from development to disease. Developmental dynamics : an official publication of the American Association of Anatomists 99 25523132
2012 Significance of EpCAM and TROP2 expression in non-small cell lung cancer. World journal of surgical oncology 86 22482828
2023 Targeting Trop-2 in cancer: Recent research progress and clinical application. Biochimica et biophysica acta. Reviews on cancer 80 37121444
2022 TROP2 Expression Across Molecular Subtypes of Urothelial Carcinoma and Enfortumab Vedotin-resistant Cells. European urology oncology 79 35216942
2022 Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Frontiers in oncology 78 36620535
1995 The epithelial/carcinoma antigen EGP-1, recognized by monoclonal antibody RS7-3G11, is phosphorylated on serine 303. International journal of cancer 76 7635574
2022 Trop-2 as a Therapeutic Target in Breast Cancer. Cancers 73 36497418
2013 Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway. Oncogene 69 23416980
2024 Trop2-targeted therapies in solid tumors: advances and future directions. Theranostics 64 38948057
2022 Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer. BMC cancer 64 36153494
2021 Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis. Neoplasia (New York, N.Y.) 52 33839455
2023 Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 50 36939530
2023 TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer. Journal of nanobiotechnology 50 37932752
2024 TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non-Small Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 49 38048058
2018 TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway. Oncology reports 48 30431125
2018 Curcumin inhibits cell proliferation and motility via suppression of TROP2 in bladder cancer cells. International journal of oncology 47 29901071
2016 TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells. Biochemical and biophysical research communications 47 26773504
2022 Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. Breast cancer research and treatment 46 35789445
2023 Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma. Human pathology 44 37977513
2019 Photoimmunotherapy targeting biliary-pancreatic cancer with humanized anti-TROP2 antibody. Cancer medicine 43 31674732
2024 ImmunoPET imaging of Trop2 in patients with solid tumours. EMBO molecular medicine 40 38565806
2024 Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. Histopathology 39 38196202
2011 Imaging of prostate cancer with immuno-PET and immuno-SPECT using a radiolabeled anti-EGP-1 monoclonal antibody. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 38 21865288
2024 Trop2-targeted therapy in breast cancer. Biomarker research 37 39135109
2022 Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates. American journal of cancer research 36 35530278
2018 Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma. PLoS pathogens 34 29538454
2023 TROP-2 directed antibody-drug conjugates (ADCs): The revolution of smart drug delivery in advanced non-small cell lung cancer (NSCLC). Cancer treatment reviews 32 37230055
2022 Trop-2 in Upper Tract Urothelial Carcinoma. Current oncology (Toronto, Ont.) 32 35735421
2020 Matriptase Cleaves EpCAM and TROP2 in Keratinocytes, Destabilizing Both Proteins and Associated Claudins. Cells 31 32326212
2023 Targeting Trop2 by Bruceine D suppresses breast cancer metastasis by blocking Trop2/β-catenin positive feedback loop. Journal of advanced research 30 37271476
2018 TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling. Molecular medicine reports 30 29845216
2024 Assessment of TROP2, CEACAM5 and DLL3 in metastatic prostate cancer: Expression landscape and molecular correlates. NPJ precision oncology 29 38760413
2023 Metastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study. Clinical genitourinary cancer 29 37344281
2023 ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers. European journal of nuclear medicine and molecular imaging 29 37792026
2018 Trop-2 plasticity is controlled by epithelial-to-mesenchymal transition. Carcinogenesis 29 30010814
2024 68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer. The Journal of clinical investigation 27 39509246
2013 TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 26 23397225
2023 Epigenetically upregulating TROP2 and SLFN11 enhances therapeutic efficacy of TROP2 antibody drug conjugate sacitizumab govitecan. NPJ breast cancer 25 37567892
2001 A novel mutation in the M1S1 gene responsible for gelatinous droplike corneal dystrophy. Investigative ophthalmology & visual science 25 11687514
2024 Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: mechanisms, clinical applications, and future directions. Frontiers in immunology 24 39555080
2018 TROP2 methylation and expression in tamoxifen-resistant breast cancer. Cancer cell international 24 30002602
2023 Antibody-drug conjugates (ADCs) targeting TROP-2 in lung cancer. Expert opinion on biological therapy 23 36995069
2000 Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy: the P501T of BIGH3 gene found in a family with gelatinous drop-like corneal dystrophy. American journal of ophthalmology 23 11004271
2023 TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development. Cancer letters 22 37268280
2003 A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy. American journal of ophthalmology 22 12614764
2025 Spatial Expression of HER2, NECTIN4, and TROP-2 in Muscle-Invasive Bladder Cancer and Metastases: Implications for Pathological and Clinical Management. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 40086591
2024 Current Status and Future Prospects of TROP-2 ADCs in Lung Cancer Treatment. Drug design, development and therapy 21 39525044
2023 Targeting Trop2 in solid tumors: a look into structures and novel epitopes. Frontiers in immunology 21 38179054
2022 TROP2 (trophoblast cell-surface antigen 2): a drug target for breast cancer. Expert opinion on therapeutic targets 21 35962580
2006 A novel TACSTD2 gene mutation in a Turkish family with a gelatinous drop-like corneal dystrophy. Molecular vision 21 17167402
2016 v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1. Cancer research 20 27634768
2014 Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis. Cell death & disease 19 24651436
2023 Trop-2 is a ubiquitous and promising target in pancreatic adenocarcinoma. Clinics and research in hepatology and gastroenterology 18 36878461
2024 Intraoperative evaluation of tumor margins using a TROP2 near-infrared imaging probe to enable human breast-conserving surgery. Science translational medicine 17 39413161
2023 Immunohistochemical expression of TROP‑2 (TACSTD2) on the urothelial carcinoma of the urinary bladder and other types of cancer. Oncology letters 17 38020299
2022 EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice. Biology open 17 35730316
2022 Alteration of Trop-2 expression in breast cancer cells by clinically used therapeutic agents and acquired tamoxifen resistance. Breast cancer (Tokyo, Japan) 17 35882754
2020 Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC. International journal of biological macromolecules 17 32768481
2023 Decoding TROP2 in breast cancer: significance, clinical implications, and therapeutic advancements. Frontiers in oncology 16 37954074
2021 The Rise of the TROP2-Targeting Agents in NSCLC: New Options on the Horizon. Oncology 16 34280931
2004 Compound heterozygous mutations of M1S1 gene in gelatinous droplike corneal dystrophy. American journal of ophthalmology 16 15013888
2025 ImmunoPET imaging of Trop2 expression in triple-negative breast cancer using [64Cu]Cu-NOTA-Trodelvy-F(ab')2. European journal of nuclear medicine and molecular imaging 15 39994021
2025 Evolution of TROP2: Biological insights and clinical applications. European journal of medicinal chemistry 15 40517574
2024 Trop-2 expression and the tumor immune microenvironment in cervical cancer. Gynecologic oncology 15 38723340
2022 TROP2 Down-regulated DSG2 to Promote Gastric Cancer Cell Invasion and Migration by EGFR/AKT and DSG2/PG/β-Catenin Pathways. Current cancer drug targets 15 35392784
2023 The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance. International journal of molecular sciences 14 38203255
2021 Trop2 Expression in Extramammary Paget's Disease and Normal Skin. International journal of molecular sciences 14 34299325
2020 Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation. BMC cancer 14 32854652
2010 Identification and characterization of a novel TACSTD2 mutation in gelatinous drop-like corneal dystrophy. Molecular vision 14 20454699
2025 Antitumor Activity and Biomarker Analysis for TROP2 Antibody-Drug Conjugate Datopotamab Deruxtecan in Patient-Derived Breast Cancer Xenograft Models. Clinical cancer research : an official journal of the American Association for Cancer Research 13 39585341
2024 Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic oncology 13 38981151
2024 Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook. Molecular pharmaceutics 13 39537365
2014 Trop2 gene: a novel target for cervical cancer treatment. Journal of cancer research and clinical oncology 13 24816726
2000 Rapid detection of M1S1 mutations by the protein truncation test. Investigative ophthalmology & visual science 13 10937555
2025 OBI-992, a Novel TROP2-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models. Molecular cancer therapeutics 12 39786401
2025 Pretargeted Trop-2 ImmunoPET for Rapid, Selective Detection of Pancreatic Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 12 39841860
2024 Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer. Journal of Cancer 12 38817863
2024 Immuno-PET/CT Imaging of Trop2 with [18F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 12 39542697
2021 Clinicopathologic significance of TROP2 and phospho-TROP2 in gastric cancer. Molecular and clinical oncology 12 33815794
2025 Novel Amanitin-Based Antibody-Drug Conjugates Targeting TROP2 for the Treatment of Pancreatic Cancer. Molecular cancer therapeutics 11 39564769
2025 ImmunoPET Imaging of Trop2 Expression in Bladder Cancer Using [64Cu]Cu-NOTA-Trodelvy. Molecular pharmaceutics 11 40059341
2023 TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas. Histopathology 11 36527253
2023 An assembly of TROP2-mediated signaling events. Journal of cell communication and signaling 11 37014471
2023 High levels of expression of Trop-2 in thymic epithelial tumors. Lung cancer (Amsterdam, Netherlands) 11 37573703
2021 DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers. BMC cancer 11 33882870
2020 TROP-2, 5hmC, and IDH1 Expression in Anaplastic Thyroid Carcinoma. International journal of surgical pathology 11 33289434
2012 Establishment of a human conjunctival epithelial cell line lacking the functional TACSTD2 gene (an American Ophthalmological Society thesis). Transactions of the American Ophthalmological Society 11 23818740
2004 Mutations in the membrane component, chromosome 1, surface marker 1 (M1S1) gene in gelatinous drop-like corneal dystrophy. Japanese journal of ophthalmology 11 15295654

Missed literature

Know a paper Affinage missed for TACSTD2? Flag it for the maintainers and the community.

No submissions yet.