Article

Role of microRNAs in the regulation of breast cancer stem cells

Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5942, USA.
Journal of Mammary Gland Biology and Neoplasia (Impact Factor: 5). 02/2012; 17(1):15-21. DOI: 10.1007/s10911-012-9242-8
Source: PubMed

ABSTRACT There is increasing evidence that many human cancers, including breast cancer, are driven and maintained by cancer stem cells (CSCs) which mediate tumor metastasis and contribute to treatment resistance and relapse. Our group was the first to describe "breast cancer stem cells" (BCSCs) characterized by expression of the cell surface markers ESA and CD44 and the absence of expression of the marker CD24. More recently, we have demonstrated that breast cancer cells contain subpopulations with stem cell properties that can be isolated by virtue of their expression of Aldehyde dehydrogenase (ALDH) as assessed by the Aldefluor assay. Interestingly, these markers identify overlapping, but not identical cell populations. Recent studies have suggested similarities between cancer stem cells and the epithelial mesenchymal transition (EMT) state. Our studies suggest that both normal and malignant breast stem cells exist in distinct, inter-convertible states (EMT and MET), the inter-conversion of which is regulated by microRNAs. EMT-like CSCs have a mesenchymal morphology, are largely quiescent, invasive and characterized by expression of the CSC markers CD24(-)CD44(+) and are EpCAM(-)CD49f(+). In contrast, the MET (mesenchymal epithelial transition) state of CSCs is characterized by active self-renewal and expression of the CSC markers ALDH and EpCAM(+)CD49f(+). A subpopulation of cells expressing both CD24(-)CD44(+) and ALDH may represent cells in transition between these states. This transition is regulated by signals originating in the microenvironment which in turn modulate microRNA networks in the CSC populations. The existence of multiple stem cell states suggests the necessity of developing therapeutic strategies capable of effectively targeting CSCs in all of these states. In addition, since CSC states are regulated by miRNAs, these small non-coding RNAs may be useful therapeutic agents to target CSCs.

Download full-text

Full-text

Available from: Shawn G Clouthier, Jul 28, 2015
2 Followers
 · 
165 Views
  • Source
    • "The symbiosis between a CAF and an epithelial cancer cell leads to various epigenetic events, coordinated by cell-cell signaling through various cytokines or even vesicle-like structures known as exosomes [29] [64]. The cancer cell may acquire a stem-like characteristic after having lost apical-basal polarity, reproducing the exact epithelial-to-mesenchymal transition found in embryogenesis and wound healing [19] [53] [76]. Several cytokines, initially described in embryology and recently in oncology, such as the chemokine CXCL12 or SDF-1α, and its co-receptor, CXCR4, appear to play a salient role in breast cancer metastasis to the brain, lung and vertebral bodies [71] [89]. "
  • Source
    • "Accumulating evidence indicates that miRNAs play important roles in regulating tumor progression [30] [31]. Although till now, there are few reports about miRNA expression profiles for NSCLC CSCs/CSLCs, many researches have published miRNA expression profiles in breast and prostate CSCs/CSLCs [32] [33]. According to experimental results from Liu et al. [33], although CSCs/CSLCs from different cell types exhibited overall distinct miRNA expression profiles, all CSCs/CSLCs commonly express certain miRNAs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies indicate that tumor maintenance, metastasis and drug-resistance are mainly conduced by a small subset of cancer cells which are termed cancer stem cells (CSCs) or cancer stem-like cells (CSLCs). Successful identification of CSCs/CSLCs might lead to discovery of the novel and effective therapeutic targets for cancers. In our study, lung CSCs/CSLCs were enriched by sphere-forming assay. Screening and selection of specific binding peptides for lung CSCs/CSLCs were performed with bacterial surface display method. Selected peptide named HCBP-1 exhibited highest specific binding capability as examined by flow cytometry and fluorescence microscopy. Drug-resistant lung CSCs/CSLCs might be characterized with HCBP-1 peptide and several microRNAs related to the stem-like properties were discriminatively expressed in HCBP-1+ subpopulation. Moreover, at least two distinct subpopulations in H460 tumor sphere cells could be distinguished by HCBP-1 peptide. Thus, a new method was established to identify lung CSCs/CSLCs, which provided robust approaches for the research of CSCs/CSLCs.
    Cancer Letters 08/2014; DOI:10.1016/j.canlet.2014.05.004 · 5.02 Impact Factor
  • Source
    • "Using a squamous cell carcinoma model, it was reported that miR-138 regulated EMT by targeting multiple components of the EMT pathways, such as ZEB2 and the epigenetic regulator EZH2. Both are repressors of E-cadherin expression (Liu et al. 2012a,b). miR-191 was downregulated in FAs, FTC, and follicular variant of PTCs by targeting CDK6, a serine–threonine kinase involved in the control of cell cycle progression (Colamaio et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid cancer is one of the most rapidly increasing malignancies. The reasons for this increase is not completely known, but increases in the diagnosis of papillary thyroid microcarcinomas and follicular variant of papillary thyroid carcinomas along with the enhanced detection of well differentiated thyroid carcinomas are probably all contributing factors. Although most cases of well differentiated thyroid carcinomas are associated with an excellent prognosis, a small percentage of patients with well differentiated thyroid carcinomas as well as most patients with poorly differentiated and anaplastic thyroid carcinomas have recurrent and/or metastatic disease that is often fatal. The cancer stem cell model suggests that a small number of cells within a cancer, known as cancer stem-like cells, are responsible for resistance to chemotherapy and radiation therapy, as well as for recurrent and metastatic disease.. In this review we will focus on current studies about thyroid cancer stem-like cells, the processes of epithelial to mesenchymal transition, and mesenchymal to epithelial transition that provide plasticity to cancer stem-like cell growth in addition to the role of microRNAs in cancer stem cell development and regulation. Understanding the biology of cancer stem cells, epithelial to mesenchymal transition and the metastatic cascade should lead to the design of more rational targeted therapies for highly aggressive and fatal thyroid cancers.
    Endocrine Related Cancer 04/2014; 21(5). DOI:10.1530/ERC-14-0002 · 4.91 Impact Factor
Show more