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miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT

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 dist...

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Autores principales: Xiang, Xiaoyu, Zhuang, Xiaoying, Jiang, Hong, Ju, Songwen, Mu, Jingyao, Zhang, Lifeng, Miller, Donald, Grizzle, William, Zhang, Huang-Ge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139014/
https://www.ncbi.nlm.nih.gov/pubmed/21460854
http://dx.doi.org/10.1038/onc.2011.54
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author Xiang, Xiaoyu
Zhuang, Xiaoying
Jiang, Hong
Ju, Songwen
Mu, Jingyao
Zhang, Lifeng
Miller, Donald
Grizzle, William
Zhang, Huang-Ge
author_facet Xiang, Xiaoyu
Zhuang, Xiaoying
Jiang, Hong
Ju, Songwen
Mu, Jingyao
Zhang, Lifeng
Miller, Donald
Grizzle, William
Zhang, Huang-Ge
author_sort Xiang, Xiaoyu
collection PubMed
description 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.
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spelling pubmed-41390142014-08-20 miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT Xiang, Xiaoyu Zhuang, Xiaoying Jiang, Hong Ju, Songwen Mu, Jingyao Zhang, Lifeng Miller, Donald Grizzle, William Zhang, Huang-Ge Oncogene Article 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. 2011-04-04 2011-08-04 /pmc/articles/PMC4139014/ /pubmed/21460854 http://dx.doi.org/10.1038/onc.2011.54 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Xiang, Xiaoyu
Zhuang, Xiaoying
Jiang, Hong
Ju, Songwen
Mu, Jingyao
Zhang, Lifeng
Miller, Donald
Grizzle, William
Zhang, Huang-Ge
miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title_full miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title_fullStr miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title_full_unstemmed miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title_short miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT
title_sort mir-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing emt
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139014/
https://www.ncbi.nlm.nih.gov/pubmed/21460854
http://dx.doi.org/10.1038/onc.2011.54
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