Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers  

作　　者：Daisong Wang Xin Hu Chunye Liu Yingying Jia Yiqin Bai Cheguo Cai Jingqiang Wang Lanyue Bai Ruikai Yang ChangDong Lin Yi-Rong Liu Shan Li Feng Qiao Ling Yao Li Chen Gaoxiang Ge Hai Jiang Dianfan Li Lin Li JianFeng Chen Zhi-Ming Shao Yi Arial Zeng 

机构地区：[1]State Key Laboratory of Cell Biology,CAS Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China [2]Key Laboratory of Breast Cancer in Shanghai,Department of Breast Surgery,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Key Laboratory of Systems Biology,Innovation Center for Cell Signaling Network,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200032,China [4]State Key Laboratory of Molecular Biology,National Center for Protein Science Shanghai,Shanghai Science Research Center,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

出　　处：《Cell Research》2019年第10期832-845,共14页细胞研究（英文版）

基　　金：grants from National Natural Science Foundation of China(31830056,31861163006,31625020,31530045,31661143043 to Y.A.Z,81874113 to Z.-M.S;81672601,81872137 to X.H.);Chinese Academy of Sciences(XDA12020378 to Y J.and XDB19000000 to Y.A.Z.);Shanghai Municipal Science and Technology Commission(17XD1404000 to Y.A.Z.)and National Ten Thousand Talents Program(to Y.A.Z.).

摘　　要：Breast cancer is a heterogeneous disease.In particular,triple-negative breast cancer(TNBC)comprises various molecular subgroups with unclear identities and currently has few targeted treatment options.Our previous study identified protein C receptor(Procr)as a surface marker on mammary stem cells(MaSCs)located in the basal layer of the normal mammary gland.Given the possible connection of TNBC with basal layer stem cells,we conducted comparative analyses of Procr in breast cancers of mouse and human origin.In mouse mammary tumors,we showed that Procr+cells are enriched for cancer stem cells(CSCs)in Wnt1 basal-like tumors,but not in Brea basal-like tumors or PyVT luminal tumors.In human cancers,PROCR was robustly expressed in half of TNBC cases.Experiments with patient-derived xenografts(PDXs)revealed that PROCR marks CSCs in this discrete subgroup(referred to as PROCR+TNBC).Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers,arrested tumor growth and prevented rapid tumor recurrence.Our data suggest a key role of MaSC in breast tumorigenesis.Moreover,our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.

关 键 词：BREAST CANCERS treatment 

分 类 号：R73[医药卫生—肿瘤]