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
Affiliations
Taichi Isobe
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Shigeo Hisamori
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Daniel J Hogan
Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
Maider Zabala
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
David G Hendrickson
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States
Piero Dalerba
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States; Department of Medicine, Division of Oncology, Stanford University, Stanford, United States
Shang Cai
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Ferenc Scheeren
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Angera H Kuo
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Shaheen S Sikandar
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Jessica S Lam
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Dalong Qian
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Frederick M Dirbas
Department of Surgery, Stanford University School of Medicine, Stanford, United States
George Somlo
City of Hope Cancer Center, Duarte, United States
Kaiqin Lao
Applied Biosystems, Foster City, United States
Patrick O Brown
Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
Michael F Clarke
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
Yohei Shimono
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
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.
