ArticleEndocrine2021
Gene expression profile of epithelial-mesenchymal transition mediators in papillary thyroid cancer.
Article in Endocrine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Thyroid cancer-derived exosomal SPP1 promotes tumor progression by driving macrophage M2 polarization through the CD44/JAK2/STAT3 signaling pathway.Organogenesis · 2026Article
- Role of epithelial-mesenchymal markers in predicting metastasis of papillary thyroid carcinoma: A retrospective case-control study.Qatar medical journal · 2025Article
- Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation ofInternational journal of molecular sciences · 2024Article
- Bioinformatics analysis of human kallikrein 5 (Cancer innovation · 2023Article
- Non-viral gene coating modified IOL delivering PDGFR-α shRNA interferes with the fibrogenic process to prevent posterior capsular opacification.Regenerative biomaterials · 2023Article
- Characterization and clinical relevance of PDGFRA pathway copy number variation gains across human cancers.Molecular genetics and genomics : MGG · 2022Article
- DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy.International journal of endocrinology · 2022Article
- Identification of Ferroptosis-Associated Long Noncoding RNA Prognostic Model and Tumor Immune Microenvironment in Thyroid Cancer.Journal of immunology research · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposePlatelet derived growth receptor alpha (PDGFRA) promotes the epithelial-mesenchymal transition (EMT) in thyroid follicular cells and is linked to lymphatic metastases in papillary thyroid cancer (PTC). We probed the regulatory network of genes linked to PDGFRA and EMT, comparing matched patient primary tumor and metastatic specimens, as well as engineered cell lines and ex vivo primary cultures with and without PDGFRA.
methodsFreshly isolated thyroid tumors with or without metastases, with matching neighboring benign or normal tissue, was isolated for comparative transcriptional analysis using a TaqMan Low Density array (TLDA) assay with genes representing important markers of EMT, cellular adhesion, apoptosis, differentiation, senescence, and signal transduction pathways in thyroid cancer. Transfected primary cultures and immortalized cell lines were also analyzed with respect to PDGFRA expression and cell phenotype.
resultsWe reveal the consistent upregulation of serine protease DPP4 and structural protein SPP1 with the progression of PTC to metastatic disease, as well as with PDGFRA expression. Conversely, epithelial integrity gene TFF3 and transcription factor SOX10 were strongly down-regulated. This gene network also includes important mediators of EMT including DSG1, MMP3, MMP9, and BECN. We observed similar genomic changes in ex vivo normal thyroid cells transfected with PDGFRA that also exhibited a partially dedifferentiated phenotype. In particular, we observed lamellopodia with induction of PDGFRA and illustrate that DPP4 and SPP1 were upregulated in this process, with decreased TFF3 and SOX10 as seen in tissue specimens. PDGFRA did decrease nuclear protein levels of differentiation factor TTF1, but not the transcription of TTF1 and PAX8.
conclusionsWe demonstrate that PDGFRA activates EMT pathways and decreases expression of genes favoring epithelial integrity, pushing follicular cells toward a dedifferentiated phenotype. SPP1 and DPP4, previously linked with adverse outcomes in thyroid cancer, appear to be regulated by PDGFRA. PDGFRA expression promotes metastatic disease through multiple EMT levers that favor formation of an invasive phenotype and increased metalloproteinase expression.
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