Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
Department of Urology, Drum Tower Hospital Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
J Hematol Oncol. 2022 Jul 14;15(1):93. doi: 10.1186/s13045-022-01312-5.
Bladder cancer is the most common malignant tumor of the urinary system. Surgical resection and chemotherapy are the two mainstream treatments for bladder cancer. However, the outcomes are not satisfactory for patients with advanced bladder cancer. There is a need to further explore more effective targeted therapeutic strategies.
Proteomics were performed to compare protein expression differences between human bladder cancer tissues and adjacent normal tissues. The function of GPD1 on bladder cancer cells were confirmed through in vivo and in vitro assays. Transcriptomics and metabolomics were performed to reveal the underlying mechanisms of GPD1. Virtual screening was used to identify allosteric activator of GPD1.
Here, we used proteomics to find that GPD1 expression was at low levels in bladder cancer tissues. Further investigation showed that GPD1 overexpression significantly promoted apoptosis in bladder cancer cells. Based on transcriptomics and metabolomics, GPD1 promotes Ca influx and apoptosis of tumor cells via the lysoPC-PAFR-TRPV2 axis. Finally, we performed a virtual screening to obtain the GPD1 allosteric activator wedelolactone and demonstrated its ability to inhibit bladder tumor growth in vitro and in vivo.
This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer.
膀胱癌是泌尿系统最常见的恶性肿瘤。手术切除和化疗是膀胱癌的两种主流治疗方法。然而，对于晚期膀胱癌患者，治疗效果并不理想。因此，需要进一步探索更有效的靶向治疗策略。
通过蛋白质组学比较人膀胱癌组织和相邻正常组织之间的蛋白表达差异。通过体内和体外实验证实 GPD1 对膀胱癌细胞的作用。通过转录组学和代谢组学揭示 GPD1 的潜在作用机制。通过虚拟筛选鉴定 GPD1 的别构激活剂。
本研究通过蛋白质组学发现 GPD1 在膀胱癌组织中表达水平较低。进一步研究表明，GPD1 过表达可显著促进膀胱癌细胞凋亡。基于转录组学和代谢组学，GPD1 通过溶酶体 PC-PAFR-TRPV2 轴促进 Ca2+内流和肿瘤细胞凋亡。最后，我们进行了虚拟筛选，获得了 GPD1 的别构激活剂 wedelolactone，并证明了其在体外和体内抑制膀胱癌肿瘤生长的能力。
本研究表明，GPD1 可能在膀胱癌中作为一种新型肿瘤抑制因子发挥作用。GPD1 的药理学激活可能是膀胱癌的一种潜在治疗方法。
