Metabolic characterization of sphere‐derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance

Yuanyuan Luo; Jiachuan Yu; Zhikun Lin; Xiaolin Wang; Jinhui Zhao; Xinyu Liu; Wangshu Qin; Guowang Xu

doi:10.1002/ijc.34967

journal article Apr 22, 2024

Metabolic characterization of sphere‐derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance

Yuanyuan Luo

Jiachuan Yu Zhikun Lin Xiaolin Wang

International Journal of Cancer Vol. 155 No. 4 pp. 742-755 · Wiley

View at Publisher Save 10.1002/ijc.34967

Abstract

AbstractAlteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs. Urea cycle is the most significantly altered metabolic pathway in PCSCs, the key metabolites arginine and proline are evidently elevated. Proline promotes cancer stem‐like characteristics via the JAK2/STAT3 signaling pathway. Meanwhile, the enzyme pyrroline‐5‐carboxylate reductase 1 (PYCR1), which catalyzes the conversion of pyrroline‐5‐carboxylic acid to proline, is highly expressed in PCSCs, and the inhibition of PYCR1 suppresses the stem‐like characteristics of prostate cancer cells and tumor growth. In addition, carnitine and free fatty acid levels are significantly increased, indicating reprogramming of fatty acid metabolism in PCSCs. Reduced sphingolipid levels and increased triglyceride levels are also observed. Collectively, our data illustrate the comprehensive landscape of the metabolic reprogramming of PCSCs and provide potential therapeutic strategies for prostate cancer.

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Details

Published: Apr 22, 2024
Vol/Issue: 155(4)
Pages: 742-755
License: View

Authors

Y

Yuanyuan Luo

CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian China; State Key Laboratory of Medical Proteomics Beijing China; Liaoning Province Key Laboratory of Metabolomics Dalian China; University of Chinese Academy of Sciences Beijing China

J

Jiachuan Yu

Department of Anesthesiology The First Affiliated Hospital of Dalian Medical University Dalian China

Z

Zhikun Lin