Over the past several decades the traditional view of cancer being a homogeneous mass of rapid proliferating malignant
cells is being replaced by a model of ever increasing complexity, which points out that cancers are complex tissues
composed of multiple cell types. A large variety of immune and other host cells constitute the tumor microenvironment,
which supports the growth and progression of the tumor where individual cancer cells evolve with increasing phenotypic
and genetic heterogeneity. Furthermore, it has also become clear that, in addition to this cellular and genetic heterogeneity,
most tumors exhibit a hierarchical organization composed of tumor cells displaying divergent lineage markers and at the
apex of this hierarchy are cells capable of self-renewal. These “cancer stem cells” not only drive tumor growth, but also mediate
metastasis and contribute to treatment resistance. Besides displaying remarkable genetic and phenotypic heterogeneity,
cancer stem cells maintain plasticity to transition between mesenchymal-like (EMT) and epithelial-like (MET) states in a process regulated
by the tumor microenvironment. These stem cell state transitions may play a fundamental role in the process of tumor metastasis. In
this review, we will discuss emerging knowledge regarding the plasticity of cancer stem cells and the role that this plasticity plays in tumor
metastasis. We also discuss the implications of these findings for the development of cancer stem cell targeted therapeutics.
Keywords: Breast cancer stem cells, MET, EMT, metastasis, therapeutic resistance.
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