miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 18, 2014
- Source ID
- 10.7554/elife.01977
Entities
People
- Angera H Kuo
- Dalong Qian
- Daniel J Hogan
- David G Hendrickson
- Ferenc A. Scheeren
- Frederick M Dirbas
- George Somlo
- Jessica S Lam
- Kaiqin Lao
- Maider Zabala
- Michael F Clarke
- Patrick O. Brown
- Piero Dalerba
- Shaheen S Sikandar
- Shang Cai
- Shigeo Hisamori
- Taichi Isobe
- Yohei Shimono
Organizations
- Applied Biosystems
- California Breast Cancer Research Program
- City of Hope National Medical Center
- Fundación Alfonso Martín Escudero
- Japan Society for the Promotion of Science
- Ludwig Institute for Cancer Research
- National Institutes of Health
- Stanford University
- The Breast Cancer Research Foundation
- UK Fulbright Commission
- United States Department of Defense