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

By Y. Shimono, Robert W. Cho, N. Lobo, Piero Dalerba, Dalong Qian, M. Diehn, Huiping Liu, S. Panula, E. Chiao, F. Dirbas and 3 more. Cell, 2009

1,247 citations recorded by the source corpus.

Summary 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 non-tumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429 and miR-183-96-182 were down-regulated 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 clonogenicity 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 down-regulation of three microRNA clusters and the similar functional regulation of clonogenicity by miR-200c provide a molecular link that connects breast cancer stem cells with normal stem cells.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/56e3a0a5e6ab08cc387bc40b313fbf217824656a

How researchers see this paper

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In Cancer Research

1. R. Weinberg
2. Thomas Brabletz
3. W. Tam
4. Yibin Kang
5. Danish H Sayed
6. Harald Schuhwerk
7. Simone Brabletz
8. T. Shibue

In Molecular Biology

1. R. Weinberg
2. Thomas Brabletz
3. Simone Brabletz
4. Yibin Kang
5. Marc P. Stemmler
6. Xiawei Wei
7. Weiqi Hong
8. Yuhe Huang

In Oncology

1. R. Weinberg
2. Thomas Brabletz
3. Simone Brabletz
4. W. Tam
5. Xiawei Wei
6. Yibin Kang
7. Weiqi Hong
8. Yuhe Huang

Citations in the corpus

• Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. (2010, neutral): “However, long-term repopulation potential of hematopoietic stem cells remains severely impaired (Liu et al., 2009).”
• The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs (2009, background): “showed that both normal mammary stem cells and breast cancer stem cells show reduced expression of miR-200 family members, resulting in increased expression of Bmi1 (ref”
• Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, neutral): “Similarly, several miRNAs involved in regulating the EMT also exert control over the TIC state, including those of the miR-200 family (Shimono et al., 2009).”
• MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer (2015, neutral): “This group includes the miR-200 family [197], miR-15/16, miR-103/107, miR-128b, miR-145, and miR-335 [137].”
• The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis (2022, background): “It directly binds the Bmi1 promoter and activates Bmi1, and hence TWIST1 can upregulate BMI1.”
• MicroRNAs in development and disease. (2011, background): “Thus, as predicted, overexpression of miR-200c inhibited colony formation by BCSC, through suppression of Bmi1, and completely inhibited their tumorigenic capacity in vivo (559).”