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 ...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.展开更多
文摘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.