论文库首页  论文库
 
论文编号:
论文题目: The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b
英文论文题目: The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b
第一作者: Zhou, W; Ye, XL; Xu, J; Cao, MG; Fang, ZY; Li, LY; Guan, GH; Liu, Q; Qian, YH; Xie, D
英文第一作者: Zhou, W; Ye, XL; Xu, J; Cao, MG; Fang, ZY; Li, LY; Guan, GH; Liu, Q; Qian, YH; Xie, D
联系作者: Xie, D (reprint author), Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
英文联系作者: Xie, D (reprint author), Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 10
期: 483
页码: eeaak9557
摘要: Metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. The pathophysiological course of metastasis is mediated by the dynamic plasticity of cancer cells, which enables them to shift between epithelial and mesenchymal phenotypes through a transcriptionally regulated program termed epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET). Using a mouse model of spontaneous metastatic breast cancer, we investigated the molecular mediators of metastatic competence within a heterogeneous primary tumor and how these cells then manipulated their epithelial-mesenchymal plasticity during the metastatic process. We isolated cells from the primary mammary tumor, the circulation, and metastatic lesions in the lung in TA2 mice and found that the long noncoding RNA (lncRNA) H19 mediated EMT and MET by differentially acting as a sponge for the microRNAs miR-200b/c and let-7b. We found that this ability enabled H19 to modulate the expression of the microRNA targets Git2 and Cyth3, respectively, which encode regulators of the RAS superfamily member adenosine 5'-diphosphate (ADP) ribosylation factor (ARF), a guanosine triphosphatase (GTPase) that promotes cell migration associated with EMT and disseminating tumor cells. Decreasing the abundance of H19 or manipulating that of members in its axis prevented metastasis from grafts in syngeneic mice. Abundance of H19, GIT2, and CYTH3 in patient samples further suggests that H19 might be exploited as a biomarker for metastatic cells within breast tumors and perhaps as a therapeutic target to prevent metastasis.
英文摘要: Metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. The pathophysiological course of metastasis is mediated by the dynamic plasticity of cancer cells, which enables them to shift between epithelial and mesenchymal phenotypes through a transcriptionally regulated program termed epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET). Using a mouse model of spontaneous metastatic breast cancer, we investigated the molecular mediators of metastatic competence within a heterogeneous primary tumor and how these cells then manipulated their epithelial-mesenchymal plasticity during the metastatic process. We isolated cells from the primary mammary tumor, the circulation, and metastatic lesions in the lung in TA2 mice and found that the long noncoding RNA (lncRNA) H19 mediated EMT and MET by differentially acting as a sponge for the microRNAs miR-200b/c and let-7b. We found that this ability enabled H19 to modulate the expression of the microRNA targets Git2 and Cyth3, respectively, which encode regulators of the RAS superfamily member adenosine 5'-diphosphate (ADP) ribosylation factor (ARF), a guanosine triphosphatase (GTPase) that promotes cell migration associated with EMT and disseminating tumor cells. Decreasing the abundance of H19 or manipulating that of members in its axis prevented metastasis from grafts in syngeneic mice. Abundance of H19, GIT2, and CYTH3 in patient samples further suggests that H19 might be exploited as a biomarker for metastatic cells within breast tumors and perhaps as a therapeutic target to prevent metastasis.
刊物名称: SCIENCE SIGNALING
英文刊物名称: SCIENCE SIGNALING
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Biochemistry & Molecular Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Cell Biology
影响因子: 6.494
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有