Novel Roles for ERK5 and Cofiin as Critical Mediators Linking Estrogen Receptor -Driven Transcription, Actin Reorganization and Invasiveness in Breast cancer

Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ER)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor- determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ER-gene transcription.

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Madak-Erdogan Z, Ventrella R, Petry L, Katzenellenbogen BS