CARM1 drives triple-negative breast cancer progression by coordinating with HIF1A  

作　　者：Dandan Feng Jie Gao Ruiqiong Liu Wei Liu Tianyang Gao Yunkai Yang Die Zhang Tianshu Yang Xin Yin Hefen Yu Wei Huang Yan Wang 

机构地区：[1]Key Laboratory of Cancer and Microbiome,State Key Laboratory of Molecular Oncology,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [2]Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China [3]Department of Clinical Laboratory,The Second Hospital of Shandong University,Jinan 250033,China [4]Department of Cancer Center,The Second Hospital of Shandong University,Jinan 250033,China [5]Beijing Key Laboratory of Cancer Invasion and Metastasis Research,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China

出　　处：《Protein & Cell》2024年第10期744-765,共22页蛋白质与细胞（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Grant Nos.41931291,42125707,81802816,81902882,and 82273403);Major State Basic Research Development Program of China(2022YFA1103402);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310027,2021-RC310-006);Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-018).

摘　　要：Coactivator-associated arginine methyltransferase 1(CARM1)promotes the development and metastasis of estro-gen receptor alpha(ERa)-positive breast cancer.The function of CARM1 in triple-negative breast cancer(TNBC)is still unclear and requires further exploration.Here,we report that CARM1 promotes proliferation,epithelial-mesen-chymal transition,and stemness in TNBC.CARM1 is upregulated in multiple cancers and its expression correlates with breast cancer progression.Genome-wide analysis of CARM1 showed that CARM1 is recruited by hypoxia-inducible factor-1 subunit alpha(HIF1A)and occupy the promoters of CDK4,Cyclin D1,β-Catenin,HIF1A,MALAT1,and SIX1 critically involved in cell cycle,HIF-1 signaling pathway,Wnt signaling pathway,VEGF signaling pathway,thereby modulating the proliferation and invasion of TNBC cells.We demonstrated that CARM1 is physically associated with and directly interacts with HIF1A.Moreover,we found that ellagic acid,an inhibitor of CARM1,can suppress the proliferation and invasion of TNBC by directly inhibiting CDK4 expression.Our research has determined the molecular basis of CARM1 carcinogenesis in TNBC and its effective natural inhibitor,which may provide new ideas and drugs for cancer therapy.

关 键 词：CARM1 HIF1A CDK4 ellagic acid TNBC 

分 类 号：R737.9[医药卫生—肿瘤]