ArticleEBioMedicine2016
PDGFRα Regulates Follicular Cell Differentiation Driving Treatment Resistance and Disease Recurrence in Papillary Thyroid Cancer.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study.International journal of molecular sciences · 2023Article
- Article
- Article
- Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer.Frontiers in endocrinology · 2022Article
- PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling.International journal of molecular sciences · 2021Article
- Gene expression profile of epithelial-mesenchymal transition mediators in papillary thyroid cancer.Endocrine · 2021Article
- AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development.Cell death & disease · 2021Article
- Review
- Blood prognostic predictors of treatment response for patients with papillary thyroid cancer.Bioscience reports · 2020Observational
- The Role of Vitamin D, Platelet-Derived Growth Factor and Insulin-Like Growth Factor 1 in the Progression of Thyroid Diseases.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies.Cancers · 2019Review
- Two distinct E3 ligases, SCFFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Development of a prognostic index based on an immunogenomic landscape analysis of papillary thyroid cancer.Aging · 2019Article
- PET Imaging of Receptor Tyrosine Kinases in Cancer.Molecular cancer therapeutics · 2018Review
- Redifferentiation of Radioiodine Refractory Differentiated Thyroid Cancer for Reapplication of I-131 Therapy.Frontiers in endocrinology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dedifferentiation of follicular cells is a central event in resistance to radioactive iodine and patient mortality in papillary thyroid carcinoma (PTC). We reveal that platelet derived growth factor receptor alpha (PDGFRα) specifically drives dedifferentiation in PTC by disrupting the transcriptional activity of thyroid transcription factor-1 (TTF1). PDGFRα activation dephosphorylates TTF1 consequently shifting the localization of this transcription factor from the nucleus to the cytoplasm. TTF1 is required for follicular cell development and disrupting its function abrogates thyroglobulin production and sodium iodide transport. PDGFRα also promotes a more invasive and migratory cell phenotype with a dramatic increase in xenograft tumor formation. In patient tumors we confirm that nuclear TTF1 expression is inversely proportional to PDGFRα levels. Patients exhibiting PDGFRα at time of diagnosis are three times more likely to exhibit nodal metastases and are 18 times more likely to recur within 5years than those patients lacking PDGFRα expression. Moreover, high levels of PDGFRα and low levels of nuclear TTF1 predict resistance to radioactive iodine therapy. We demonstrate in SCID xenografts that focused PDGFRα blockade restores iodide transport and decreases tumor burden by >50%. Focused PDGFRα inhibitors, combined with radioactive iodine, represent an additional avenue for treating patients with aggressive variants of PTC.
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