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Open Access 01-12-2022 | Research

Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis

Authors: Wenlong Zhang, Xin He, Haoli Yin, Wenmin Cao, Tingsheng Lin, Wei Chen, Wenli Diao, Meng Ding, Hao Hu, Wenjing Mo, Qing Zhang, Hongqian Guo

Published in: Journal of Hematology & Oncology | Issue 1/2022

Abstract

Background

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.

Methods

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.

Results

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 Ca²⁺ 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.

Conclusions

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.

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Title: Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis
Authors: Wenlong Zhang
Xin He
Haoli Yin
Wenmin Cao
Tingsheng Lin
Wei Chen
Wenli Diao
Meng Ding
Hao Hu
Wenjing Mo
Qing Zhang
Hongqian Guo
Publication date: 01-12-2022
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-022-01312-5

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Abstract

Background

Methods

Results

Conclusions

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