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MicroRNA-7 downregulates expression of KLF4, suppressing breast to brain metastasis



DOI:10.1038/bonekey.2013.86

Okuda et al. used a microRNA profile analysis to show that cancer stem-like cells (CSCs) carrying the cell surface marker combination CD24−/CD44+/ESA (EpCAM)+ are significantly more likely to metastasize to brain or bone tissue compared with non-CSC cells. CSCs with this profile showed reduced expression of miR-7, which enhances the expression of KLF4, a gene that encodes Kruppel-like factor 4, which is expressed by induced pluripotent stem cells.

The expression of miR-7 appears to downregulate KLF4, suppressing metastasis of breast cancer cells to brain but not to bone. Reduced expression of miR-7 causes the reverse. The authors suggest that both genes warrant further investigation as markers for brain metastasis in breast cancer, and also represent potential therapeutic targets.

Editor’s comment: This important study shows that the miR-7/KLF4 pathway is specifically involved in the metastasis of breast cancer to brain tissue. Interestingly, however, ectopic expression of miR-7 in osteotropic breast cancer stem cells also suppresses KLF4 expression, whereas it does not block experimental bone metastasis. A possible explanation is that downstream targets of the miR-7/KLF4 pathway allow these cancer stem cells to disseminate in the brain microenvironment, but not in the bone microenvironment. Thus, this study also provides insight into the importance of the host tissue and related microenvironmental factors, which can combine to create an environment hospitable for cancer stem cells.


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