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

Taichi Isobe, Shigeo Hisamori, Daniel J. Hogan, Maider Zabala, David G. Hendrickson, Piero Dalerba, Shang Cai, Ferenc Scheeren, Angera H. Kuo, Shaheen S. Sikandar, Jessica S. Lam, Dalong Qian, Frederick M. Dirbas, George Somlo, Kaiqin Lao, Patrick O. Brown, Michael F. Clarke, Yohei Shimono

研究成果: Article査読

116 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号e01977
ジャーナルeLife
3
DOI
出版ステータスPublished - 2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 免疫学および微生物学(全般)
  • 生化学、遺伝学、分子生物学(全般)

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