Abstract
Induction of epithelial-to-mesenchymal transition (EMT) in cancer stem cells (CSCs) can occur as the result of embryonic pathway signaling. Activation of Hedgehog (Hh), Wnt, Notch, or transforming growth factor-β leads to the upregulation of a group of transcriptional factors that drive EMT. This process leads to the transformation of adhesive, non-mobile, epithelial-like tumor cells into cells with a mobile, invasive phenotype. CSCs and the EMT process are currently being investigated for the role they play in driving metastatic tumor formation in breast cancer. Both are very closely associated with embryonic signaling pathways that stimulate self-renewal properties of CSCs and EMT-inducing transcription factors. Understanding these mechanisms and embryonic signaling pathways may lead to new opportunities for developing therapeutic agents to help prevent metastasis in breast cancer. In this review, we examine embryonic signaling pathways, CSCs, and factors affecting EMT.
Highlights
Breast cancer stem cells (CSCs) are increasingly thought to play a major role in breast cancer growth and the formation of metastases
Preventing the induction of epithelial-to-mesenchymal transition (EMT) in primary breast cancer may serve as a novel mechanism to potentially inhibit the spread of metastatic disease
Activation of embryonic signaling pathways and their downstream transcription factors are responsible for driving EMT, resulting in the transformation of epithelial-like CSCs into cells with aggressive mesenchymal-like phenotypes
Summary
Breast cancer stem cells (CSCs) are increasingly thought to play a major role in breast cancer growth and the formation of metastases. In the absence of additional EMT modulators in the stromal microenvironment, the cell transforms back to the original epithelial phenotype (via MET) [76] This important concept suggests that transcription of the E-cadherin gene, or post-translational modification, may be partly controlled by epigenetic mechanisms. Extensive cross-talk among these transcription factors is necessary to maintain mesenchymal cell phenotypes [85] These EMT-inducing transcription factors play a role in acquisition of stem cell characteristics as these factors are expressed at much higher levels in CD44+/CD24- breast CSC-like cells than in more differentiated epithelial cells [44,86]. Mori and colleagues [95] reported that mouse mammary epithelial cells underwent malignant transformation, including loss of cell-to-cell contact, when exposed to long-term oxidative stress
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