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

التفاصيل البيبلوغرافية
العنوان: Metabolic characterization of sphere-derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance.
المؤلفون: Luo Y; 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., Yu J; Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China., Lin Z; 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., Wang X; 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., Zhao J; 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., Liu X; 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., Qin W; 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., Xu G; 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.
المصدر: International journal of cancer [Int J Cancer] 2024 Aug 15; Vol. 155 (4), pp. 742-755. Date of Electronic Publication: 2024 Apr 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 1995- : New York, NY : Wiley-Liss
Original Publication: 1966-1984 : Genève : International Union Against Cancer
مواضيع طبية MeSH: Prostatic Neoplasms*/metabolism , Prostatic Neoplasms*/pathology , Neoplastic Stem Cells*/metabolism , Neoplastic Stem Cells*/pathology , Pyrroline Carboxylate Reductases*/metabolism , Urea*/metabolism , delta-1-Pyrroline-5-Carboxylate Reductase*, Male ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Signal Transduction ; Janus Kinase 2/metabolism ; Metabolomics/methods ; Proline/metabolism ; STAT3 Transcription Factor/metabolism ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Cell Proliferation ; Lipidomics/methods
مستخلص: Alteration 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.
(© 2024 UICC.)
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معلومات مُعتمدة: 21934006 National Natural Science Foundation of China; 32100626 National Natural Science Foundation of China; 2022RQ026 Dalian Science and Technology Talent Innovation Support Program
فهرسة مساهمة: Keywords: JAK2‐STAT3; cancer stem cells; lipidomics; metabolomics; prostate cancer
المشرفين على المادة: EC 1.5.1.- (Pyrroline Carboxylate Reductases)
8W8T17847W (Urea)
EC 1.5.1.2 (delta-1-Pyrroline-5-Carboxylate Reductase)
EC 2.7.10.2 (Janus Kinase 2)
9DLQ4CIU6V (Proline)
0 (STAT3 Transcription Factor)
EC 2.7.10.2 (JAK2 protein, human)
0 (STAT3 protein, human)
تواريخ الأحداث: Date Created: 20240422 Date Completed: 20240619 Latest Revision: 20240619
رمز التحديث: 20240619
DOI: 10.1002/ijc.34967
PMID: 38647131
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-0215
DOI:10.1002/ijc.34967