Figure 6. Indirect pharmacological inhibition of FASN promotes a phenotypic switch in breast tumorsphere architecture.

Left. Figure shows representative light microscope representations of 3rd generation mammospheres formed by MCF10DCIS.com cells growing in sphere medium in the absence or presence of graded concentrations of metformin, as specified (20× magnifications). Right. Quantification of the hollow (luminal-like) and filled/mass (basal-like) morphologies occurring in untreated and metformin-treated P3 mammospheres. Note that long-term exposure to clinically relevant nanomolar concentrations of the indirect FASN inhibitor metformin reduces the intra-sphere heterogeneity and promotes a switch from basal- to luminal-like sphere morphologies, suggesting promotion of a luminal differentiation axis and/or reversion of the basal/mesenchymal state.