ERα-Mediated Nuclear Sequestration of RSK2 Is Required for ER⁺ Breast Cancer Tumorigenesis.

ABSTRACT: Although ribosomal protein S6 kinase A3 (RSK2) activation status positively correlates with patient responses to antiestrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of estrogen receptor-positive (ER⁺) breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N terminus to activate a proneoplastic transcriptional network critical to the ER⁺ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status. ER⁺ tumor growth was strongly dependent on nuclear RSK2,

SUBMITTER: Ludwik KA 

PROVIDER: S-EPMC9011919 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature