Snail-1 Overexpression Correlates with Metastatic Phenotype in BRAFV600E Positive Papillary Thyroid Carcinoma
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The ability of cancer to metastasize is regulated by various signaling pathways, including transforming growth factor β (TGFβ), also implicated in the upregulation of Snail-1 transcription factor in malignant neoplasms. B-type Raf kinase gene (BRAF)V600E, the most common driving mutation in papillary thyroid carcinoma (PTC), induces epithelial to mesenchymal transition (EMT) in thyroid cancer cells through changes in the Snail-1 level, increasing cell migration and invasion. However, little is known about the mechanism of Snail-1 and BRAFV600E relations in humans. Our study included 61 PTC patients with evaluated BRAFV600E mutation status. A total of 18 of those patients had lymph node metastases—of whom 10 were BRAFV600E positive, and 8 negative. Our findings indicate that the expression of Snail-1, but not TGFβ1, correlates with the metastatic phenotype in PTC. This is the first piece of evidence that the upregulation of Snail-1 corresponds with the presence of BRAFV600E mutation and increased expression of Snail-1 in metastatic PTC samples is dependent on BRAFV600E mutation status.
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Upregulation of pioneer developmental organizers such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, and BCL6 is reported downstream of BRAF/MAPK-driven tumor.
“Even upregulation of pioneer developmental organizers, such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, BCL6, et al., are reported downstream of BRAF/MAPK-driven tumor, the pathways causing lineage reprogramming are not clear12,15,30–36.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [36]
The Discussion (page unavailable) reports higher Snail-1 expression specifically in metastatic papillary thyroid carcinomas with a BRAFV600E mutation, and suggests that the mutation may facilitate its overexpression. The paper does not report BRAF/MAPK-driven upregulation of SOX2, KLF4, β-catenin, c-MYC, TBX3, or BCL6, or establish the broader downstream relationship claimed. (LLM, conf=0.88)
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Cites
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Cited by
Sorted by citations
Zhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14 · see citing works
“Even upregulation of pioneer developmental organizers, such as SOX2, KLF4, β -catenin, SNAIL-1, c-MYC, TBX3, BCL6, et al., are reported downstream of BRAF/MAPK-driven tumor, the pathways causing lineage reprogramming are not clear 12,15,30 – 36 .”
Background
- Authors
- Wieczorek-Szukala, K., Kopczynski, J., Kowalska, A., & Lewinski, A.
- Affiliations
- Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93-338 Lodz, Poland
- Department of Pathology, Holy Cross Cancer Center, 25-734 Kielce, Poland
- Jan Kochanowski University (PL)
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2020-08-21
- Volume
- 9
- Issue
- 9
- Pages
- 2701
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC7565998
- OpenAlex
- W3063492462
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- SNAI1, BRAF V600E mutation, papillary thyroid carcinoma, lymph node metastasis, epithelial-mesenchymal transition, TGF-β1, metastatic phenotype, gene overexpression, cell migration and invasion
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