To mimic a 3D‐tumour environment, we next employed our spheroid model and found that ECM rigidity and high cell density of H1299control spheroids activated NANOG in the central core (Fig EV4B), but this was completely absent from H1299RASSF1A, implying that the artificially stiff ECM that can activate NANOG in H1299RASSF1A (Fig 5A) is not achieved under more physiological conditions (Fig 5D). This evidence concerns the gene NANOG and neoplasm.