Under hypoxic conditions, Seven in Absentia homologue 2 (SIAH2), an E3 ligase with a RING domain, is the regulator of proteasome degradation of NRF1 (Nuclear Respiratory Factor 1) and, therefore, switches TAM polarization to the tumor-promoting M2 state in breast cancer (66). This evidence concerns the gene NRF1 and breast carcinoma.