Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer  

作　　者：Shuaishuai Teng Yang Eric Li Ming Yang Rui Qi Yiming Huang Qianyu Wang Yanmei Zhang Shanwen Chen Shasha Li Kequan Lin Yang Cao Qunsheng Ji Qingyang Gu Yujing Cheng Zai Chang Wei Guo Pengyuan Wang Ivan Garcia-Bassets Zhi John Lu Dong Wang 

机构地区：[1]MOE Key Lab of Bioinformatics,Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing 100084,China [2]MOE Key Lab of Bioinformatics,Center for Synthetic and Systems Biology,School of Life Sciences,Tsinghua University,Beijing,China [3]Ludwig Institute for Cancer Research,9500 Gilman Drive,La Jolla,CA 92093,USA [4]PKU-THU Center for Life Sciences,Tsinghua University,Beijing,China [5]Division of General Surgery,Peking University First Hospital,Peking University,Beijing,China [6]WuXi AppTec(Shanghai)Co.,Ltd.,Shanghai 200131,China [7]Zhejiang University-University of Edinburgh Institute,Haining,China [8]School of Medicine,University of California,San Diego,La Jolla,CA,USA [9]Collaborative Innovation Center for Biotherapy,West China Hospital,Sichuan University,Chengdu,China [10]School of Basic Medical Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China

出　　处：《Cell Research》2020年第1期34-49,共16页细胞研究（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China(81673460,31771461,81972798);funding from Tsinghua-Peking Joint Center for Life Sciences,Beijing Municipal Science&Technology Commission and Fok Ying-Tong Education Foundation;This study was also supported by Beijing Advanced Innovation Center for Structural Biology and Bio-Computing Platform of Tsinghua University Branch of China National Center for Protein Sciences(Beijing);I.G.B.is supported by the U.S.Department of Defense(W81XWH-14-1-0089 and W81XWH-12-1-0358);the Ovarian Cancer Research Fund Alliance(Liz Tilberis Award)bequest from the Estate of Agatha Pepper Fort.

摘　　要：Metastasis,the development of secondary malignant growths at a distance from a primary tumor,is the cause of death for 90%of cancer patients,but little is known about how metastatic cancer cells adapt to and colonize new tissue environments.Here,using clinical samples,patient-derived xenograft(PDX)samples,PDX cells,and primary/metastatic cell lines,we discovered that liver metastatic colorectal cancer(CRC)cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program.We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers.Further,we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription,thereby driving CRC liver metastasis.Importantly,similar transcription reprogramming can be observed in multiple cancer types.Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.

关 键 词：METASTASIS COLORECTAL cancer 

分 类 号：R735.34[医药卫生—肿瘤]