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Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination

Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, 01-813 Warsaw, Poland
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Genetics, 02-781 Warsaw, Poland
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 02-109 Warsaw, Poland
Clinic of Endocrinological and General Surgery, Medical University of Łódź, 91-513 Łódź, Poland
Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, 02-781 Warsaw, Poland
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5619;
Received: 8 October 2019 / Revised: 6 November 2019 / Accepted: 7 November 2019 / Published: 10 November 2019
(This article belongs to the Special Issue Cell and Molecular Biology of Thyroid Disorders 2.0)
It is well known that Prospero homeobox 1 (PROX1) is a crucial regulator of lymphangiogenesis, that reprograms blood endothelial cells to lymphatic phenotype. However, the role of PROX1 in tumor progression, especially in angiogenesis remains controversial. Herein, we studied the role of PROX1 in angiogenesis in cell lines derived from follicular thyroid cancer (FTC: FTC-133) and squamous cell carcinoma of the thyroid gland (SCT: CGTH-W-1) upon PROX1 knockdown. The genes involved in angiogenesis were selected by RNA-seq, and the impact of PROX1 on vascularization potential was investigated using human umbilical vein endothelial cells (HUVECs) cultured in conditioned medium collected from FTC- or SCT-derived cancer cell lines after PROX1 silencing. The angiogenic phenotype was examined in connection with the analysis of focal adhesion and correlated with fibroblast growth factor 2 (FGF2) levels. Additionally, the expression of selected genes involved in angiogenesis was detected in human FTC tissues. As a result, we demonstrated that PROX1 knockdown resulted in upregulation of factors associated with vascularization, such as metalloproteinases (MMP1 and 3), FGF2, vascular endothelial growth factors C (VEGFC), BAI1 associated protein 2 (BAIAP2), nudix hydrolase 6 (NUDT6), angiopoietin 1 (ANGPT1), and vascular endothelial growth factor receptor 2 (KDR). The observed molecular changes resulted in the enhanced formation of capillary-like structures by HUVECs and upregulated focal adhesion in FTC-133 and CGTH-W-1 cells. The signature of selected angiogenic genes’ expression in a series of FTC specimens varied depending on the case. Interestingly, PROX1 and FGF2 showed opposing expression levels in FTC tissues and seven thyroid tumor-derived cell lines. In summary, our data revealed that PROX1 is involved in the spreading of thyroid cancer cells by regulation of angiogenesis. View Full-Text
Keywords: PROX1; angiogenesis; follicular thyroid cancer PROX1; angiogenesis; follicular thyroid cancer
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Rudzińska, M.; Mikula, M.; Arczewska, K.D.; Gajda, E.; Sabalińska, S.; Stępień, T.; Ostrowski, J.; Czarnocka, B. Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination. Int. J. Mol. Sci. 2019, 20, 5619.

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