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Elife. 2014 Nov 18;3. doi: 10.7554/eLife.01977.

miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
2
Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States.
3
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
4
Department of Surgery, Stanford University School of Medicine, Stanford, United States.
5
City of Hope Cancer Center, Duarte, United States.
6
Applied Biosystems, Foster City, United States.

Abstract

MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression.

KEYWORDS:

APC; WNT signaling pathway; breast cancer; cancer stem cells; cell biology; human; human biology; medicine; miR-142; miR-150; mouse

PMID:
25406066
PMCID:
PMC4235011
DOI:
10.7554/eLife.01977
[Indexed for MEDLINE]
Free PMC Article

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