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 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

作者机构：MOE Key Lab of Bioinformatics Department of Basic Medical Sciences School of Medicine Tsinghua University Beijing 100084 China MOE Key Lab of Bioinformatics Center for Synthetic and Systems Biology School of Life Sciences Tsinghua University Beijing China Ludwig Institute for Cancer Research 9500 Gilman Drive La Jolla CA 92093 USA MOE Key Lab of Bioinformatics Center for Synthetic and Systems Biology School of Life Sciences Tsinghua University Beijing China PKU-THU Center for Life Sciences Tsinghua University Beijing China Division of General Surgery Peking University First Hospital Peking University Beijing China WuXi AppTec(Shanghai)Co. Ltd. Shanghai 200131 China Zhejiang University-University of Edinburgh Institute Haining China School of Medicine University of California San Diego La Jolla CA USA MOE Key Lab of Bioinformatics Department of Basic Medical Sciences School of Medicine Tsinghua University Beijing 100084 China Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University Chengdu China School of Basic Medical SciencesChengdu University of Traditional Chinese Medicine Chengdu 611137 China 

出 版 物：《细胞研究（英文版）》 (Cell Research)

年 卷 期：2020年第30卷第1期

页      面：34-49页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：We thank Yusheng Wu and Prof.Xuerui Yang (Tsinghua University,China) for help with cell proliferation assay.We thank Qian Gao for help with HiSeq 1500 operation.We thank members of the Tsinghua University Animal Resources Center for their care of the mice.The results published here are in whole or p(81673460,31771461,81972798) funding from Tsinghua-Peking Joint Center for Life Sciences,Beijing Municipal Science & Technology Commission and Fok YingTong Education Foundation.This study was also supported by Beijing Advanced Innovation Center for Structural Biology and Bio-Computing Platform of Tsinghua University Branch of C(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 

主　　题：Colorectal cancer Metastasis 

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 ***,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 *** showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and ***,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 ***,similar transcription reprogramming can be obsenved in multiple cancer *** data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.