Abstract
The prospero homeobox 1 (Prox1) transcription factor is a key player during embryogenesis and lymphangiogenesis. Altered Prox1 expression has been found in a variety of human cancers, including papillary thyroid carcinoma (PTC). Interestingly, Prox1 may exert tumor suppressive or tumor promoting effect, depending on the tissue context. In this study, we have analyzed Prox1 expression in normal and malignant human thyroid carcinoma cell lines. Moreover, we determined the effect of Prox1 silencing and overexpression on the cellular processes associated with the metastatic potential of tumor cells: proliferation, migration, invasion, apoptosis and anchorage-independent growth, in the follicular thyroid carcinoma (FTC) FTC-133 cell line. We found that Prox1 expression was significantly higher in FTC-derived cells than in PTC-derived cells and normal thyroid, and it was associated with the PI3K/Akt signaling pathway. In the FTC-133 cells, it was associated with cell invasive potential, motility and wound closure capacities, but not with proliferation or apoptosis. Modifying Prox1 expression also induced substantial changes in the cytoskeleton structure and cell morphology. In conclusion, we have shown that Prox1 plays an important role in the development of FTC and that its suppression prevents, whereas its overexpression promotes, the malignant behavior of thyroid follicular cancer cells.
Highlights
Differentiated thyroid carcinoma (DTC) originates from thyroid follicular cells and is the most common endocrine malignancy
We analyzed the expression levels and distribution of prospero homeobox 1 (Prox1) in four thyroid cancer cell lines: TPC1 and BcPAP derived from papillary thyroid carcinoma, and FTC-133 and CGTH-W-1 derived from follicular thyroid carcinoma, as well as in the normal thyroid normal thyroid follicular cells (NTHY) cell line, using quantitative real-time reverse transcriptionPCR (Q-RT-PCR), Western blot and immunofluorescent analyses
In the two follicular thyroid carcinoma cell lines: FTC-133 and CGTH, the protein levels detected by Western blot paralleled the results of Q-RT-PCR, with strong bands corresponding to the protein detected in both cell lines
Summary
Differentiated thyroid carcinoma (DTC) originates from thyroid follicular cells and is the most common endocrine malignancy. Two major DTC histopathological types: papillary (PTC) and follicular thyroid carcinoma (FTC), account for up to 90% of all thyroid tumor cases. PTC has a tendency to metastasize to regional lymph nodes and disseminate through lymphatic vasculature, whereas FTC rather via the circulatory system. Identifying molecular markers of the lymphatic endothelial cells and lymphatic signaling factors has facilitated studies of their impact on the tumor growth and metastasis. Well-known markers of lymphatic cells include the mucine-type transmembrane glycoprotein podoplanin, hyaluronian receptor LYVE-1, and vascular endothelial growth factor receptor 3 (VEGFR-3) as well as the prospero homeobox 1 (Prox1) transcription factor [1,2,3,4]
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