Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression

Despite recent medical advances, metastasis, tumor relapse and resistance to therapy remain the principal causes of death for breast cancer patients. The lack of effective therapies calls for an improved understanding of the molecular mechanisms driving breast cancer progression. It is increasingly acknowledged that aberrant activation of a latent embryonic program - known as the epithelial-mesenchymal transition (EMT) - can endow cancer cells with the migratory and invasive capabilities associated with metastatic competence [1-3]. Moreover, several lines of evidence have converged in recent years to support the notion that not all cancer cells within a given tumor are equal in terms of their tumor-initiating potential. The emerging paradigm posits that tumor progression is driven by a small subpopulation of cancer cells - termed cancer stem cells (CSCs) or tumor-initiating cells - that exhibit two defining characteristics: the ability to self-renew and the ability to regenerate the phenotypic heterogeneity of the parental tumor [4]. CSCs have thus been implicated both in initiating and sustaining primary tumor growth and in driving the seeding and establishment of metastases at distal sites [5-9].Whereas the CSC hypothesis does not stipulate the cell of origin for a particular cancer, it is reasonable to hypothesize that tumors may originate from the transformation of normal adult tissue stem cells or from more differentiated progenitors that have acquired self-renewal capabilities [4] (Figure 1). Importantly, recent studies have established a crucial link between passage through EMT and the acquisition of molecular and functional properties of stem cells [10,11]. Thus, in addition to bestowing migratory and invasive potential, induction of EMT in immortalized and transformed human mammary epithelial cells significantly enhanced their self-renewal and tumor-initiating capabilities and led to the expression of stem-cell markers, typically associated with breast CSCs