EwS morphological cell state displays context-specific plasticity. A schematic representing findings. High EF1-expressing EwS cells show a change in morphological state or organization according to seeding site or location within a cluster. Low expression of EF1 causes a shift towards more protrusive cell state and reduced sensitivity to some tissue environmental cues but not others, suggesting EF1 enables site-specific specialization of cancer cells. In contrast, non-transformed fibroblasts display highly heterogeneous cell morphologies regardless of extrinsic cues.