ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Post-Chornobyl thyroid papillary carcinomas display distinct pastScientific reports · 2026Article
- Diverse roles of SERPINE1 in regulating cellular proliferation and invasion.International journal of oncology · 2026Article
- Article
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- SIX5-activated LINC01468 promotes lung adenocarcinoma progression by recruiting SERBP1 to regulate SERPINE1 mRNA stability and recruiting USP5 to facilitate PAI1 protein deubiquitylation.Cell death & disease · 2022Article
- Whole-exome sequencing and bioinformatic analyses revealed differences in gene mutation profiles in papillary thyroid cancer patients with and without benign thyroid goitre background.Frontiers in endocrinology · 2022Article
- INI1-Deficient Thyroid Carcinoma is an Aggressive Disease with Epithelioid and Rhabdoid Phenotype. A Case Report, Survey of INI1 Expression in Thyroid Lesions and Literature Review.Head and neck pathology · 2021Review
- Transcriptome analysis of sinensetin-treated liver cancer cells guided by biological network analysis.Oncology letters · 2021Article
- Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.International journal of molecular sciences · 2021Review
- Notch Signaling in Thyroid Cancer.Advances in experimental medicine and biology · 2021Review
- Six-gene signature for predicting survival in patients with head and neck squamous cell carcinoma.Aging · 2020Article
- Down-Regulation ofFrontiers in oncology · 2020Article
- Article
- Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation.Oncogene · 2019Article
- Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma.Endocrine connections · 2019Article
- Robust analysis of novel mRNA-lncRNA cross talk based on ceRNA hypothesis uncovers carcinogenic mechanism and promotes diagnostic accuracy in esophageal cancer.Cancer management and research · 2019Article
- The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1.Cell death & disease · 2018Article
- Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway.Molecular oncology · 2018Article
- The Role ofThe oncologist · 2018Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeNotch1, a transmembrane receptor, has been recently shown to aid in the determination of thyroid cell fate associated with tumorigenesis. This study aimed to investigate the clinical relevance of Notch1 and its role in the regulation of differentiated thyroid cancer (DTC) behavior. EXPERIMENTAL
designWe examined Notch1 expression level and its relationship with clinicopathologic features and outcomes of DTC. Notch1 intracellular domain (NICD) was further characterized both in vitro and in vivo by gain-of-function assays using an inducible system.
resultsNotch1 expression levels were downregulated in primary DTC tissue samples compared with contralateral nontumor and benign thyroid tissues. Decreased Notch1 expression in DTC was associated with advanced patient age (P = 0.032) and the presence of extrathyroidal invasion (P = 0.005). Patients with lower Notch1 expression had a significantly higher recurrence rate (P = 0.038). Restoration of NICD in a stably doxycycline-inducible metastatic DTC cell line reduced cell growth and migration profoundly. Using an orthotopic thyroid cancer model, NICD induction significantly reduced the growth of the primary thyroid tumor and inhibited the development of lung metastasis. Serpin peptidase inhibitor, clade E, member 1 (SERPINE1) was discovered by microarray as the most significant gene downregulated by NICD. Further validation showed that the induction of NICD reduced SERPINE1 expression in a dose-dependent manner, whereas restoration of a relative higher level of SERPINE1 was observed with NICD back to minimal level. In addition, SERPINE1 knock-down inhibited DTC cell migration.
conclusionsNotch1 regulates the aggressive phenotypes of DTC, which could be mediated by SERPINE1 inhibition. Notch1/SERPINE1 axis warrants further investigation as a novel therapeutic target for advanced DTC. Clin Cancer Res; 22(14); 3582-92. ©2016 AACR.
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