Abstract
The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells—CGTH-W-1—were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of PROX1 depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of PROX1-depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells.
Highlights
Metastasis is a complex multistep biological process during which cancer cells leave the site of the primary tumour and migrate to distant anatomic sites where they proliferate and form secondary tumour foci
While prospero homeobox 1 (PROX1) expression is associated with tumour development and metastasis, its exact function in the process of tumorigenesis remains unclear
We reported previously levels of PROX1 mRNA in follicular thyroid carcinoma-derived cells as compared to cells derived from papillary thyroid cancer that may relate to follicular thyroid cancer progression and enhanced invasion [37]
Summary
Metastasis is a complex multistep biological process during which cancer cells leave the site of the primary tumour and migrate to distant anatomic sites where they proliferate and form secondary tumour foci. Even though the mechanisms and pathways of cancer development and spreading have been extensively studied, the mechanisms of one of the most critical steps in cancer progression associated with a worse prognosis—infiltration of adjacent tissues by malignant tumours and spreading to form distant metastasis—remains to be elucidated. One of the working models of cancer spreading highlights the crucial role of the lymphatic system, which is in accordance with its basic function in the defence of the organism against various diseases and in the development of inflammatory states [1,2]. PROX1 is of particular interest among these markers because it plays an essential role in other biological processes, such as cell differentiation, proliferation, migration and apoptosis
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