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

Research output: Contribution to journal › Article › peer-review

164 Citations (Scopus)

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.

Original language	English
Article number	e01977
Journal	eLife
Volume	3
DOIs	https://doi.org/10.7554/eLife.01977
Publication status	Published - 18-11-2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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, Article 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",

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day = "18",

doi = "10.7554/eLife.01977",

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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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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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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