TGF-β-mediated regulation of plasminogen activators is human telomerase reverse transcriptase dependent in cancer...

Telomerase is a specialized reverse transcriptase/terminal transferase enzyme that adds telomeric repeat sequences at the extreme end of a newly replicated chromosome. Apart from telomere lengthening, telomerase has many extracurricular activities. Telomerase is known to regulate the expression of many genes and helps in cancer progression and epithelial-to-mesenchymal transitions (EMTs). We have previously reported that human telomerase reverse transcriptase (hTERT) regulates the expression of plasminogen activator such as urokinase-type plasminogen activator (uPA) in cancer cells following a genome-wide transcriptomic study. Here, we present data substantiating these results in terms of real-time assays, western blots, and immunofluorescence. Another aim of this study is to find out the possible mechanism by which hTERT regulates the expression of plasminogen activators. We have used some molecular biology techniques such as quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence and some assays such as wound healing assay and colony formation assay to solve this question. In this study, we show a positive association between hTERT and uPA. We also demonstrate that hTERT enhances uPA expression concomitant with EMT. Knocking down of hTERT reduces uPA expression as well as reverses EMT in cancer cells. We have also found that uPA is a transforming growth factor beta (TGF-β)-induced protein. Our observations establish that TGF-β-induced uPA expression is hTERT dependent.