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Int J Biol Sci 2023; 19(15):4726-4743. doi:10.7150/ijbs.85893 This issue Cite

Research Paper

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer

Ming-kun Chen^1,2,3#, Zhuo-Yu Xiao^2,3,6#, Zhi-Peng Huang^2,3#, Kang-Yi Xue^2,3, Hui Xia^2,3, Jia-Wei Zhou^2,3, De-Ying Liao^2,3, Zhi-Jian Liang^2,3, Xiao Xie^2,3, Qing-Zhu Wei⁴, Lin Zhong⁴, Jian-Kun Yang^2,3, Cun-Dong Liu^2,3✉, Yang Liu^2,3,5✉, Shan-Chao Zhao^1,2,3✉

1. Department of Urology, NanFang Hospital, Southern Medical University, Guangzhou, 510515, China.
2. Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China.
3. The Third Clinical College of Southern Medical University, Guangzhou, 510630, China.
4. Department of Pathology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China.
5. Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150007, China.
6. Medical College of Shaoguan University, Shaoguan, 512026, China.
^# These authors contributed equally to this work.

✉ Corresponding authors: Shan-Chao Zhao, Department of Urology, Nangfang Hospital, Southern Medical University, Guangzhou, 510515, China. Tel: 13794399828, Email: lulululuedu.cn. Yang Liu, Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630 (PR China). Tel: 18620092639, Email: 1037900334com. Cun-dong Liu, Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630 (PR China). Email: 290185262com. More

Abstract

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Keywords: Glycine decarboxylase (GLDC), Glycolytic metabolism, Metastasis, Immune escape, Prostate cancer

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