Single-cell analysis revealing the metabolic landscape of prostate cancer  

作　　者：Jing Wang He-Kang Ding Han-Jiang Xu De-Kai Hu William Hankey Li Chen Jun Xiao Chao-Zhao Liang Bing Zhao Ling-Fan Xu 

机构地区：[1]Department of Urologic Oncology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230031,China [2]Department of Urology,The First Affiliated Hospital of Anhui Medical University,Hefei 230001,China [3]Institute of Urology,Anhui Medical University,Hefei 230001,China [4]Anhui Province Key Laboratory of Genitourinary Diseases,Anhui Medical University,Hefei 230001,China [5]Department of Genetics,University of North Carolina,Chapel Hill,NC 27599,USA [6]Department of Geriatrics,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China [7]Department of Urology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China

出　　处：《Asian Journal of Andrology》2024年第5期451-463,共13页亚洲男性学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81902611,82272886,and 82200484);USTC Research Funds of the Double First-Class Initiative(YD9110002041);the Natural Science Foundation of Anhui Education Department(No.2022AH030118).

摘　　要：Tumor metabolic reprogramming is a hallmark of cancer development,and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer(CRPC)treatment.Nevertheless,treatment failure inevitably occurs,largely due to cellular heterogeneity,which cannot be deciphered by traditional bulk sequencing techniques.By employing computational pipelines for single-cell RNA sequencing,we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells.Moreover,we identified that neuroendocrine(NE)cells tend to have high metabolic rates,which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer(NEPC),one of the most lethal variants of prostate cancer(PCa).Additionally,we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells.These results establish a detailed metabolic landscape of PCa,highlight a potential mechanism of disease progression,and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

关 键 词：cancer heterogeneity cancer metabolism GLUTAMINE prostate cancer single-cell sequencing 

分 类 号：R737.25[医药卫生—肿瘤]