Breast cancer is the most common cancer diagnosis worldwide accounting for 1 out of every 8 cancer diagnoses. The elevated expression of Thymidine Kinase 1 (TK1) is associated with more aggressive tumor grades, including breast cancer. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement in breast cancer has not been identified. Here, we evaluate potential pathogenic effects of elevated TK1 expression by comparing HCC 1806 to HCC 1806 TK1-knockdown cancer cells (L133). Transcriptomic profiles of HCC 1806 and L133 cells showed cell cycle progression, apoptosis, and invasion as potential pathogenic pathways affected by TK1 expression. Subsequent in-vitro studies confirmed differences between HCC 1806 and L133 cells in cell cycle phase progression, cell survival, and cell migration. Expression comparison of several factors involved in these pathogenic pathways between HCC 1806 and L133 cells identified p21 and AKT3 transcripts were significantly affected by TK1 expression. Creation of a protein-protein interaction map of TK1 and the pathogenic factors we evaluated predict that the majority of factors evaluated either directly or indirectly interact with TK1. Our findings argue that TK1 elevation directly increases HCC 1806 cell pathogenicity and is likely occurring by p21- and AKT3-mediated mechanisms to promote cell cycle arrest, cellular migration, and cellular survival.

中文翻译：

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TK1 表达通过 HCC 1806 乳腺癌细胞的细胞周期进程、细胞迁移和细胞存活影响致病性。

乳腺癌是全球最常见的癌症诊断，占每 8 例癌症诊断中就有 1 例。胸苷激酶 1 (TK1) 表达升高与更具侵袭性的肿瘤分级相关，包括乳腺癌。最近的研究表明TK1可能参与癌症的发病机制；然而，其与乳腺癌的直接关系尚未确定。在这里，我们通过比较 HCC 1806 与 HCC 1806 TK1 敲低癌细胞 (L133) 来评估 TK1 表达升高的潜在致病作用。HCC 1806 和 L133 细胞的转录组谱显示细胞周期进展、细胞凋亡和侵袭是受 TK1 表达影响的潜在致病途径。随后的体外研究证实了 HCC 1806 和 L133 细胞在细胞周期阶段进展、细胞存活和细胞迁移方面的差异。对 HCC 1806 和 L133 细胞之间参与这些致病途径的几个因子进行表达比较，发现 p21 和 AKT3 转录本受到 TK1 表达的显着影响。创建 TK1 的蛋白质-蛋白质相互作用图谱和我们评估的致病因素预测，评估的大多数因素直接或间接与 TK1 相互作用。我们的研究结果表明，TK1 升高直接增加 HCC 1806 细胞的致病性，并且可能通过 p21 和 AKT3 介导的机制发生，从而促进细胞周期停滞、细胞迁移和细胞存活。