Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Urology, The Fifth Hospital of Wuhan, Wuhan, China.
Cancer Lett. 2018 Feb 1;414:278-293. doi: 10.1016/j.canlet.2017.11.015. Epub 2017 Nov 24.
Transmembrane-4-L-Six-Family-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate cell development, growth and motility. Here we show that TM4SF1 is strongly upregulated in human muscle invasive bladder cancer (MIBC) tissues, corroborating the bioinformatical results of transcriptome analysis. Moreover, tissue microarray (TMA) shows significant correlations (p < 0.05) between high expression of TM4SF1 and T stage, TNM stage, lymph node metastasis status and survival rate of MIBC patients, indicating a positive association between TM4SF1 expression and poorer prognosis. Furthermore, in vitro and in vivo studies indicate that the proliferation of human bladder cancer (BCa) cells is significantly suppressed by knockdown of TM4SF1 (p < 0.05). Functionally, the reduction of TM4SF1 could induce cell cycle arrest and apoptosis possibly via the upregulation of reactive oxygen species (ROS) in BCa cells. In addition, these observations could be recovered by treatment with GW9662 (antagonist of PPARγ) and resveratrol (activator of SIRT1). Taken together, our results suggest that high expression of TM4SF1 predicts poor prognosis of MIBC.
跨膜 4 结构域家族 1（TM4SF1）是 L6 家族的成员，作为信号转导物调节细胞发育、生长和运动。在这里，我们表明 TM4SF1 在人类肌肉浸润性膀胱癌（MIBC）组织中强烈上调，与转录组分析的生物信息学结果一致。此外，组织微阵列（TMA）显示 TM4SF1 高表达与 T 分期、TNM 分期、淋巴结转移状态和 MIBC 患者生存率之间存在显著相关性（p<0.05），表明 TM4SF1 表达与预后不良之间存在正相关。此外，体外和体内研究表明，TM4SF1 敲低显著抑制人膀胱癌（BCa）细胞的增殖（p<0.05）。功能上，TM4SF1 的减少可能通过上调 BCa 细胞中的活性氧（ROS）诱导细胞周期停滞和细胞凋亡。此外，这些观察结果可以通过用 GW9662（PPARγ 拮抗剂）和白藜芦醇（SIRT1 激活剂）处理来恢复。总之，我们的研究结果表明，TM4SF1 的高表达预示着 MIBC 的预后不良。
