Take ATF1 for example, in the process of neural signals in TME steering cancer stemness’ establishing the hierarchical structures of malignant cells, ATF1 enhances cancer stemness by simultaneously activating both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thus driving nuclear reconfiguration and mitochondrial renewal across various cancer types including BC (26). The gene discussed is NRF1; the disease is cancer.