Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
Sci Rep. 2017 Jul 12;7(1):5249. doi: 10.1038/s41598-017-05489-5.
Cell migration drives cell invasion and metastatic progression in prostate cancer and is a major cause of mortality and morbidity. However the mechanisms driving cell migration in prostate cancer patients are not fully understood. We previously identified the cancer-associated cell migration protein Tetraspanin 1 (TSPAN1) as a clinically relevant androgen regulated target in prostate cancer. Here we find that TSPAN1 is acutely induced by androgens, and is significantly upregulated in prostate cancer relative to both normal prostate tissue and benign prostate hyperplasia (BPH). We also show for the first time, that TSPAN1 expression in prostate cancer cells controls the expression of key proteins involved in cell migration. Stable upregulation of TSPAN1 in both DU145 and PC3 cells significantly increased cell migration and induced the expression of the mesenchymal markers SLUG and ARF6. Our data suggest TSPAN1 is an androgen-driven contributor to cell survival and motility in prostate cancer.
细胞迁移驱动前列腺癌的细胞侵袭和转移进展，是导致死亡率和发病率的主要原因。然而，驱动前列腺癌患者细胞迁移的机制尚不完全清楚。我们之前发现，四跨膜蛋白 1（TSPAN1）是一种与癌症相关的细胞迁移蛋白，是前列腺癌中一种具有临床相关性的雄激素调节靶标。在这里，我们发现雄激素可以急性诱导 TSPAN1 的表达，并且在前列腺癌中相对于正常前列腺组织和良性前列腺增生（BPH）显著上调。我们还首次表明，前列腺癌细胞中的 TSPAN1 表达控制着参与细胞迁移的关键蛋白的表达。在 DU145 和 PC3 细胞中稳定上调 TSPAN1 可显著增加细胞迁移并诱导间充质标志物 SLUG 和 ARF6 的表达。我们的数据表明，TSPAN1 是雄激素驱动的前列腺癌细胞存活和运动的贡献者。
