ArticleNeoplasia (New York, N.Y.)2021
Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.
Article in Neoplasia (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Dynamic modulation of intercellular adhesion mediated by matriptase-EPCAM/Trop-2 axes is critical for cell extrusion, division, and collective migration.Cell adhesion & migration · 2026Article
- Trop-1/EpCAM Thr115 is a driver of hyperproliferative cell repair and of severe lung damage in COVID-19.iScience · 2026Article
- TROP2 antibody-drug conjugate: unique epitope engagement drives differentiated efficacy.Antibody therapeutics · 2026Article
- ADC Target Profiling in NSCLC: Generalizable AI Separates TROP-2 and cMET Phenotypes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer.Translational lung cancer research · 2026Review
- Expression of Nectin-4 and Trop-2 in upper tract urothelial carcinoma: implications for biomarker-driven antibody-drug conjugate therapy.The journal of pathology. Clinical research · 2026Article
- Adipocyte-derived estrogen signaling influences TROP2 expression in ERα-positive breast cancer.Frontiers in endocrinology · 2026Article
- Extracellular Domain Shedding of TROP2 Activates EGFR Signaling to Drive Prostate Cancer Metastasis.Cancer research · 2025Article
- Epigenetic drivers of metalloproteinases and metastasis.Trends in cell biology · 2025Review
- Expanding the potential of antibody-drug conjugates in gastrointestinal malignancies: beyond HER2 targets.ESMO gastrointestinal oncology · 2025Review
- Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome.Chemical reviews · 2025Review
- Novel Amanitin-Based Antibody-Drug Conjugates Targeting TROP2 for the Treatment of Pancreatic Cancer.Molecular cancer therapeutics · 2025Article
- Large, recursive membrane platforms are associated to Trop-1, Trop-2, and protein kinase signaling for cell growth.Molecular biology of the cell · 2025Article
- Resistance to antibody-drug conjugates: A review.Acta pharmaceutica Sinica. B · 2025Review
- Circ_0096710 facilitates tumor growth via controlling ADAM10 expression in esophageal squamous cell carcinoma.Thoracic cancer · 2025Article
- Review
- Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook.Molecular pharmaceutics · 2024Review
- Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth.Pharmaceutics · 2024Article
- Comparison of Anti-Trop2 Extracellular Domain Antibodies Generated Against Peptide and Protein Immunogens for Targeting Trop2-Positive Tumour Cells.Applied biochemistry and biotechnology · 2024Article
- Progress and Innovative Combination Therapies in Trop-2-Targeted ADCs.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. No Trop-2 cleavage was detected in normal human tissues, whereas most tumors showed Trop-2 cleavage, including skin, ovary, colon, and breast cancers. Coimmunoprecipitation and mass spectrometry analysis revealed that ADAM10 physically interacts with Trop-2. Immunofluorescence/confocal time-lapse microscopy revealed that the two molecules broadly colocalize at the cell membrane. We show that ADAM10 inhibitors, siRNAs and shRNAs abolish the processing of Trop-2, which indicates that ADAM10 is an effector protease. Proteolysis of Trop-2 at R87-T88 triggered cancer cell growth both in vitro and in vivo. A corresponding role was shown for metastatic spreading of colon cancer, as the R87A-T88A Trop-2 mutant abolished xenotransplant metastatic dissemination. Activatory proteolysis of Trop-2 was recapitulated in primary human breast cancers. Together with the prognostic impact of Trop-2 and ADAM10 on cancers of the skin, ovary, colon, lung, and pancreas, these data indicate a driving role of this activatory cleavage of Trop-2 on malignant progression of tumors.
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