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

doi:10.7554/eLife.01977

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: ジャーナルへの寄稿 › 学術論文 › 査読

166 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	英語
論文番号	e01977
ジャーナル	eLife
巻	3
DOI	https://doi.org/10.7554/eLife.01977
出版ステータス	出版済み - 18-11-2014
外部発表	はい

All Science Journal Classification (ASJC) codes

神経科学一般
生化学、遺伝学、分子生物学一般
免疫学および微生物学一般

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.7554/eLife.01977

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Isobe, T., Hisamori, S., Hogan, D. J., Zabala, M., Hendrickson, D. G., Dalerba, P., Cai, S., Scheeren, F., Kuo, A. H., Sikandar, S. S., Lam, J. S., Qian, D., Dirbas, F. M., Somlo, G., Lao, K., Brown, P. O., Clarke, M. F., & Shimono, Y. (2014). miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. eLife, 3, 記事 e01977. https://doi.org/10.7554/eLife.01977

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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. ",

keywords = "APC, WNT signaling pathway, breast cancer, cancer stem cells, cell biology, human, human biology, medicine, miR-142, miR-150, mouse",

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

year = "2014",

month = nov,

day = "18",

doi = "10.7554/eLife.01977",

language = "English",

volume = "3",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

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Isobe, T, Hisamori, S, Hogan, DJ, Zabala, M, Hendrickson, DG, Dalerba, P, Cai, S, Scheeren, F, Kuo, AH, Sikandar, SS, Lam, JS, Qian, D, Dirbas, FM, Somlo, G, Lao, K, Brown, PO, Clarke, MF & Shimono, Y 2014, 'miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway', eLife, vol. 3, e01977. https://doi.org/10.7554/eLife.01977

TY - JOUR

T1 - miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway

AU - Isobe, Taichi

AU - Hisamori, Shigeo

AU - Hogan, Daniel J.

AU - Zabala, Maider

AU - Hendrickson, David G.

AU - Dalerba, Piero

AU - Cai, Shang

AU - Scheeren, Ferenc

AU - Kuo, Angera H.

AU - Sikandar, Shaheen S.

AU - Lam, Jessica S.

AU - Qian, Dalong

AU - Dirbas, Frederick M.

AU - Somlo, George

AU - Lao, Kaiqin

AU - Brown, Patrick O.

AU - Clarke, Michael F.

AU - Shimono, Yohei

PY - 2014/11/18

Y1 - 2014/11/18

N2 - 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.

AB - 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.

KW - APC

KW - WNT signaling pathway

KW - breast cancer

KW - cancer stem cells

KW - cell biology

KW - human

KW - human biology

KW - medicine

KW - miR-142

KW - miR-150

KW - mouse

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U2 - 10.7554/eLife.01977

DO - 10.7554/eLife.01977

M3 - Article

C2 - 25406066

AN - SCOPUS:84936848998

SN - 2050-084X

VL - 3

JO - eLife

JF - eLife

M1 - e01977

ER -

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

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All Science Journal Classification (ASJC) codes

UN SDG

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