miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT.
miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT.
复制标题
DOI：
10.1038/onc.2011.54
复制
发表时间：
2011-08-04
期刊：
影响因子：
8
通讯作者：
Zhang, H-G
中科院分区：
文献类型：
--
作者：
Xiang, X.;Zhuang, X.;Ju, S.;Zhang, S.;Jiang, H.;Mu, J.;Zhang, L.;Miller, D.;Grizzle, W.;Zhang, H-G
miR-155是一种微小RNA，在包括乳腺癌在内的许多类型的癌细胞中过表达，其在肿瘤转移中的作用研究非常有限。肿瘤转移是一个多步骤的过程，该过程的最后一步是在远离原发肿瘤部位的器官中形成肉眼可见的肿瘤。这一步是研究得最少的。在这里，我们报告了miR-155在4 T1乳腺肿瘤细胞中的稳定表达显著降低了肿瘤细胞播散的侵袭性，这是由于阻止了体内肿瘤细胞的上皮向间质转化（EMT）。此外，miR-155直接抑制转录因子TCF 4的表达，TCF 4是EMT的重要调节因子。然而，当肿瘤细胞直接注射到血流中时，miR-155显著促进肺中的宏观肿瘤形成。基因表达谱分析鉴定了一组与促进肺部肉眼可见肿瘤形成相关的基因。重要的是，这些基因中的大多数在上皮细胞中过表达。我们的发现为miR-155如何调节肿瘤转移的发展提供了新的见解。这项研究表明，过表达miR-155的肿瘤细胞的位置是一个关键因素：在乳腺脂肪垫中，miR-155可防止肿瘤扩散;而在肺中，miR-155显然维持了肿瘤细胞的上皮表型，这对肉眼可见的肿瘤形成至关重要。
miR-155, a micro-RNA, is over-expressed in many types of cancer cells, including breast cancer, and its role(s) in tumor metastasis has been studied on a very limited basis. Tumor metastasis is a multi-step process with the last step in the process being formation of macroscopic tumor in organs distant from the primary tumor site. This step is the least studied. Here, we report that stable expression of miR-155 in 4T1 breast tumor cells reduces significantly the aggressiveness of tumor cell dissemination as a result of preventing epithelial-to-mesenchymal transition (EMT) of tumor cells in vivo. Further, miR-155 directly suppresses the expression of the transcription factor TCF4, which is an important regulator of EMT. However, when tumor cells are injected directly into the bloodstream, miR-155 remarkably promotes macroscopic tumor formation in the lung. Analysis of gene expression profiling identified a group of genes that are associated with promoting macroscopic tumor formation in the lung. Importantly, most of these genes are over-expressed in epithelial cells. Our findings provide new insight into how miR-155 modulates the development of tumor metastasis. This study suggests that the location of tumor cells over-expressing miR-155 is a critical factor: in mammary fat pads miR-155 prevents tumor dissemination; whereas in the lung miR-155 apparently maintains the epithelial phenotype of tumor cells that is critical for macroscopic tumor formation.
登录
查看更多内容
影响因子：
5.3
作者：
Kong, William;Yang, Hua;Cheng, Jin Q.
通讯作者：
Cheng, Jin Q.
影响因子：
14.9
作者：
Chung KH;Hart CC;Al-Bassam S;Avery A;Taylor J;Patel PD;Vojtek AB;Turner DL
通讯作者：
Turner DL
影响因子：
8
作者：
Cheng, CW;Wu, PE;Shen, CY
通讯作者：
Shen, CY
影响因子：
21.3
作者：
Ma, Li;Young, Jennifer;Prabhala, Harsha;Pan, Elizabeth;Mestdagh, Pieter;Muth, Daniel;Teruya-Feldstein, Julie;Reinhardt, Ferenc;Onder, Tamer T.;Valastyan, Scott;Westermann, Frank;Speleman, Frank;Vandesompele, Jo;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM