ArticleOncotarget2014
Loss of Trop2 causes ErbB3 activation through a neuregulin-1-dependent mechanism in the mesenchymal subtype of HNSCC.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- The Impact of Trophoblast Cell-Surface Antigen 2 Expression on the Survival of Patients with Gastrointestinal Tumors: A Systematic Review.Journal of personalized medicine · 2023Review
- TROP-2 is widely expressed in vulvar squamous cell carcinoma and represents a potential new therapeutic target.Journal of cancer research and clinical oncology · 2023Article
- Overview of Trop-2 in Cancer: From Pre-Clinical Studies to Future Directions in Clinical Settings.Cancers · 2023Review
- Trop2 Forms a Stable Dimer with Significant Structural Differences within the Membrane-Distal Region as Compared to EpCAM.International journal of molecular sciences · 2021Article
- Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Clinicopathologic significance of TROP2 and phospho-TROP2 in gastric cancer.Molecular and clinical oncology · 2021Article
- Trop2: Jack of All Trades, Master of None.Cancers · 2020Review
- Review
- miR-488-3p sponged by circ-0000495 and mediated upregulation of TROP2 in head and neck squamous cell carcinoma development.Journal of Cancer · 2020Article
- Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2019Article
- Down-regulation ofHepatology communications · 2018Article
- The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target.Oncotarget · 2018Review
- Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.Cell death & disease · 2018Article
- Neuregulin in Health and Disease.International journal of brain disorders and treatment · 2018Article
- TROP2 methylation and expression in tamoxifen-resistant breast cancer.Cancer cell international · 2018Article
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
- TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT.Oncotarget · 2017Article
- LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.Cancer chemotherapy and pharmacology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
In head and neck squamous cell cancer (HNSCC), four intrinsic subtypes (or groups) have been identified, and each one possesses a unique biology that will require specific treatment strategies. We previously reported that mesenchymal (group 2) tumors exhibit reduced levels of Trop2 expression. In this study, we investigated the functional role of Trop2 in HNSCC and find that loss results in autocrine activation of the EGFR family member ErbB3 via neuregulin-1. Trop2 localizes to both the cell surface and cytosol of HNSCC cells and forms a complex with neuregulin-1, which is predominantly cytosolic. Inactivation of Trop2 increases the concentration of neuregulin-1 at the cell surface where it is cleaved to activate ErbB3. In primary HNSCC, detection of ErbB3 activation was limited to Trop2 negative tumors. An analysis of the Cancer Genome Atlas (TCGA) HNSCC dataset confirms enrichment for ErbB3 activity in mesenchymal tumors. Notably, Trop2 loss triggers sensitivity to anti-ErbB3 antibodies, which results in reduced proliferation and tumorigenic growth of Trop2 negative HNSCC cancer cells. These results uncover a molecular mechanism by which tumor cells control the amount of cell-surface neuregulin-1 available for cleavage and ErbB3 activation. Moreover, we demonstrate that Trop2 is a potential surrogate biomarker to identify tumors with ErbB3 activation and may therefore respond to anti-ErbB3 therapeutics.
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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.