Cancer cell employs a microenvironmental neural signal transactivating nucleus-mitochondria coordination to acquire stemness  

作　　者：Bin He Rui Gao Shasha Lv Ailin Chen Junxiu Huang Luoxuan Wang Yunxiu Feng Jiesi Feng Bing Liu Jie Lei Bing Deng Bin He Bai Cui Fei Peng Min Yan Zifeng Wang Eric W-F Lam Bilian Jin Zhiming Shao Yulong Li Jianwei Jiao Xi Wang Quentin Liu 

机构地区：[1]State Key Laboratory of Oncology in South China,Sun Yat-sen University Cancer Center,Guangzhou 510060,PR China [2]Department of Medical Oncology,The Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 510275,PR China [3]Institute of Cancer Stem Cell,Cancer Center,Dalian Medical University,Dalian 116023,PR China [4]Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,PR China [5]State Key Laboratory of Membrane Biology,Peking University School of Life Sciences,Beijing 100871,PR China [6]Department of Surgery and Cancer,Imperial College London,London W120NN,UK [7]Department of Breast Surgery,Precision Cancer Medicine Center,Fudan University Shanghai Cancer Center,Shanghai 200032,PR China [8]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,PR China

出　　处：《Signal Transduction and Targeted Therapy》2023年第8期3818-3836,共19页信号转导与靶向治疗(英文)

基　　金：This research work was supported by the National Key R&D Program of China(2019YFA0110300 to Q.L.);the National Natural Science Foundation of China(No.82003096 to R.G.,No.82002943 to B.H.,No.81820108024 to Q.L.and No.81972594 to M.Y.);the Natural Science Foundation of Guangdong(2017A030313608 to Q.L.);the Science and Technology Planning Project of Guangzhou(201804020044 to Q.L.).

摘　　要：Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive.Here,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer stemness.Deconvolution of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.Specifically,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved hub.Upon activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial rejuvenating.Accordingly,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells.These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.

关 键 词：Cancer neural ARCHITECTURES 

分 类 号：R730[医药卫生—肿瘤]