Stemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival.

摘要: Breast cancer stem cells (CSCs) are thought to drive recurrence and metastasis. Their identity has been linked the epithelial mesenchymal transition (EMT) but remains highly controversial since--depending on cell-line studied--either (E) or (M) markers, alone together have associated with stemness. Using distinct transcript expression signatures characterizing three different E, M hybrid E/M cell-types, our data support a novel model that links mixed EM signature stemness in 1) individual cells, 2) luminal basal cell lines, 3) vivo xenograft mouse models, 4) all breast subtypes. In particular, we found co-expression of E was poorest outcome patients as well enrichment for stem-like both cell-lines. This link between explained by two findings: first, cultures showed increased cooperation mammosphere formation (indicative stemness) compared more differentiated cell-types. Second, single-cell qPCR analysis revealed genes could be co-expressed same cell. These were generated had combination several traits since they displayed plasticity, self-renewal, formation, produced ALDH1+ progenies, while less plasticity self-renewal. Thus, state reflecting its promotion E-M offers dual biological rationale robust association poor prognosis, independent cellular origin. Together, explains previous paradoxical findings CSCs appear cell-lines Our results suggest targeting heterogeneity eliminating cell-types improve patient survival cancer-subtype.