title: 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.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Taichi
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hisamori
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hogan
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Maider
authors.initials: M
authors.lastname: Zabala
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Hendrickson
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Piero
authors.initials: P
authors.lastname: Dalerba
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Shang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Scheeren
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Angera H
authors.initials: AH
authors.lastname: Kuo
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Shaheen S
authors.initials: SS
authors.lastname: Sikandar
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Lam
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Dalong
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, United States.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Dirbas
authors.affiliation: City of Hope Cancer Center, Duarte, United States.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Applied Biosystems, Foster City, United States.
authors.forename: Kaiqin
authors.initials: K
authors.lastname: Lao
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clarke
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D002999:Clone Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009940:Organoids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; C555337:APC protein, human; C555159:MIRN142 microRNA, human; C533097:MIR150, human
keywords: APC; WNT signaling pathway; breast cancer; cancer stem cells; cell biology; human; human biology; medicine; miR-142; miR-150; mouse