A study suggested that ER-α physically interacts with RKS2, resulting in the accumulation of RSK2 in nuclear sequestration, and RSK2 can promote neoplastic transformation and facilitate metastatic tumor growth of ER+ breast cancer (Ludwik et al., 2018), but there was no explanation for RSK2 expression negatively correlating with ER status. The gene discussed is ESR1; the disease is metastatic neoplasm.