ArticleGenes & development2012
Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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The trial behind it
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Who cites it
101 citing papers in PubMed, 148 citations in OpenAlex.
- 68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer.The Journal of clinical investigation · 2024Trial
- TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Disease stage-dependent expression of ADC-related biomarkers in urothelial carcinoma.Translational andrology and urology · 2026Article
- Antibody-Drug Conjugates Targeting HER2 and Trop-2: A New Force in Precision Treatment for Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bimodality in pan-cancer proteomics reveals new opportunities for biomarker discovery.Genome biology · 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
- TROP2/claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer.Journal for immunotherapy of cancer · 2026Article
- Trop2-Based Antibody-Drug Conjugates: Emerging Strategy and Progress in Triple-Negative Breast Cancer Therapy.Current oncology (Toronto, Ont.) · 2026Review
- Extracellular Domain Shedding of TROP2 Activates EGFR Signaling to Drive Prostate Cancer Metastasis.Cancer research · 2025Article
- Toxicity Profile of New Therapies in Metastatic Urothelial Carcinoma and Its Impact on Treatment Selection.Cancers · 2025Review
- Differential Localization of β-Catenin Protein in CTNNB1 Mutant Endometrial Cancers Results in Distinct Transcriptional Profiles.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- [Trop-2 expression in solid tumors : Expanded protein diagnostics within the molecular tumor board].Pathologie (Heidelberg, Germany) · 2025Article
- Correlation of TROP2 expression with clinico-pathological features and outcomes in HR+/HER2- breast cancer receiving neoadjuvant chemotherapy.The oncologist · 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
- A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan.Scientific reports · 2025Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook.Molecular pharmaceutics · 2024Review
- [Research Progress and Perspectives of Antibody-drug Conjugates Targeting Trophoblast Cell Surface Antigen-2 in Advanced Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth.Pharmaceutics · 2024Article
- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and is overexpressed in many epithelial cancers. However the biological function of Trop2 in tissue maintenance and tumorigenesis remains unclear. In this study, we demonstrate that Trop2 is a regulator of self-renewal, proliferation, and transformation. Trop2 controls these processes through a mechanism of regulated intramembrane proteolysis that leads to cleavage of Trop2, creating two products: the extracellular domain and the intracellular domain. The intracellular domain of Trop2 is released from the membrane and accumulates in the nucleus. Heightened expression of the Trop2 intracellular domain promotes stem/progenitor self-renewal through signaling via β-catenin and is sufficient to initiate precursor lesions to prostate cancer in vivo. Importantly, we demonstrate that loss of β-catenin or Trop2 loss-of-function cleavage mutants abrogates Trop2-driven self-renewal and hyperplasia in the prostate. These findings suggest that heightened expression of Trop2 is selected for in epithelial cancers to enhance the stem-like properties of self-renewal and proliferation. Defining the mechanism of Trop2 function in self-renewal and transformation is essential to identify new therapeutic strategies to block Trop2 activation in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.