Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

Yohei Shimono; Maider Zabala; Robert W. Cho; Neethan Lobo; Piero Dalerba; Dalong Qian; Maximilian Diehn; Huiping Liu; Sarita P. Panula; Eric Chiao; Frederick M. Dirbas; George Somlo; Renee A.Reijo Pera; Kaiqin Lao; Michael F. Clarke

doi:10.1016/j.cell.2009.07.011

Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

Yohei Shimono
, Maider Zabala
, Robert W. Cho
, Neethan Lobo
, Piero Dalerba
, Dalong Qian
, Maximilian Diehn
, Huiping Liu
, Sarita P. Panula
, Eric Chiao
, Frederick M. Dirbas
, George Somlo
, Renee A.Reijo Pera
, Kaiqin Lao
, Michael F. Clarke

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

1100 Citations (Scopus)

Abstract

Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

Original language	English
Pages (from-to)	592-603
Number of pages	12
Journal	Cell
Volume	138
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2009.07.011
Publication status	Published - 07-08-2009
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2009.07.011

Cite this

@article{ada2c2e253ff4ac0a4a6cbd991975fa3,

title = "Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells",

abstract = "Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.",

author = "Yohei Shimono and Maider Zabala and Cho, \{Robert W.\} and Neethan Lobo and Piero Dalerba and Dalong Qian and Maximilian Diehn and Huiping Liu and Panula, \{Sarita P.\} and Eric Chiao and Dirbas, \{Frederick M.\} and George Somlo and Pera, \{Renee A.Reijo\} and Kaiqin Lao and Clarke, \{Michael F.\}",

note = "Funding Information: We thank Andy Fire for helpful discussions and advice. We thank Jessica S. Lam for technical assistance. This work was supported by the California Breast Cancer Research Program of the University of California \#12FB-0053 to Y.S., by the Fundacion Alfonso Martin Escudero and the Fulbright to M.Z., and by the grants from the NIH (NIH CA100225, CA104987, CA126524, CA139490), the Breast Cancer Research Foundation, the Morton Family Foundation, and the Ludwig Foundation to M.F.C. Also, M.F.C. is a consultant for Oncomed Pharmaceuticals, which is developing therapeutics against cancer stem cells. ",

year = "2009",

month = aug,

day = "7",

doi = "10.1016/j.cell.2009.07.011",

language = "English",

volume = "138",

pages = "592--603",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "3",

}

TY - JOUR

T1 - Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

AU - Shimono, Yohei

AU - Zabala, Maider

AU - Cho, Robert W.

AU - Lobo, Neethan

AU - Dalerba, Piero

AU - Qian, Dalong

AU - Diehn, Maximilian

AU - Liu, Huiping

AU - Panula, Sarita P.

AU - Chiao, Eric

AU - Dirbas, Frederick M.

AU - Somlo, George

AU - Pera, Renee A.Reijo

AU - Lao, Kaiqin

AU - Clarke, Michael F.

N1 - Funding Information: We thank Andy Fire for helpful discussions and advice. We thank Jessica S. Lam for technical assistance. This work was supported by the California Breast Cancer Research Program of the University of California #12FB-0053 to Y.S., by the Fundacion Alfonso Martin Escudero and the Fulbright to M.Z., and by the grants from the NIH (NIH CA100225, CA104987, CA126524, CA139490), the Breast Cancer Research Foundation, the Morton Family Foundation, and the Ludwig Foundation to M.F.C. Also, M.F.C. is a consultant for Oncomed Pharmaceuticals, which is developing therapeutics against cancer stem cells.

PY - 2009/8/7

Y1 - 2009/8/7

N2 - Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

AB - Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

UR - https://www.scopus.com/pages/publications/68049114782

UR - https://www.scopus.com/pages/publications/68049114782#tab=citedBy

U2 - 10.1016/j.cell.2009.07.011

DO - 10.1016/j.cell.2009.07.011

M3 - Article

C2 - 19665978

AN - SCOPUS:68049114782

SN - 0092-8674

VL - 138

SP - 592

EP - 603

JO - Cell

JF - Cell

IS - 3

ER -

Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

Abstract

UN SDGs

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this