Abstract
Thymidine kinase 1 (TK1) is a well-studied cancer biomarker. It is commonly found upregulated in the serum of cancer patients, and its levels correlate with stage and grade, disease progression, and prognosis. It has recently been reported that TK1 localizes on the plasma cell membrane of hematological and solid malignancies, and not on the membrane of normal healthy cells, and while on the membrane, TK1 has enzymatic activity. However, the function of TK1 on the surface membrane is not well understood. Here, we hypothesize that it may have a role in tumor invasion and migration. It has been shown that TK1 expression levels positively correlate with epithelia to mesenchymal transition (EMT) markers in patients with breast cancer as they progress from HER2+ to triple negative breast cancer. In this study, we silenced TK1 expression by siRNA and show that TK1’s membrane expression is significantly downregulated at 60 hours post transfection. Using a Matrigel-based quantitative invasion assay, we measured cell invasion potential in cells either expressing or lacking TK1 on their membrane and found that cells that lack TK1 on their membrane exhibit decreased invasion potential. These results suggest that TK1’s presence on the membrane may play a role in invasion and cell migration in cancer.
Highlights
It has been shown that Thymidine kinase 1 (TK1) expression levels positively correlate with epithelia to mesenchymal transition (EMT) markers in patients with breast cancer as they progress from HER2+ to triple negative breast cancer
It was reported that TK1 expression levels correlate with EMT markers in breast cancer in clinical samples as the disease progresses to triple negative breast cancer [12]
Cells treated with siRNA 58 had the most dramatic silencing in TK1 surface expression with a 93.82% reduction in surface expression compared to cells treated with control siRNA
Summary
TK1 levels can increase in response to DNA damage, especially after chemotherapy and radiotherapy This increase is thought to provide cancer cells with a supply of nucleotides for DNA repair rather than for proliferation, and serves as a support mechanism to promote the survival of cancer cells [3]. While TK1 has mostly been studied as a cancer biomarker in the serum, we have recently shown that TK1 localizes on the plasma membrane of cells, this is an event independent of proliferation and appears to be exclusive to malignant cells. For these reasons, TK1 may be a novel target for cancer immunotherapy. These results suggest that TK1 may have a role in migration and immunoregulation, as well as in epithelial mesenchymal transitions (EMT)
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