👤 Serena Ventrella

We show an exceptional case of a right aortic arch (RAA) in a patient with DiGeorge syndrome, breaking the rule that the first epiaortic vessel courses to the contralateral side of the aortic arch. This is a RAA with an aberrant left subclavian artery (ALSA) and an isolated left carotid artery (ILCA) arising from the left pulmonary artery (LPA) via a left anterior ductus arteriosus (LADA), along with bilateral ductus arteriosus. This unique case highlights educational pitfalls in using a simple rule to define arch sidedness. Although challenging, echocardiographic diagnosis of such vascular anomalies is feasible in expert hands. The color-flow and Doppler pattern of the epiaortic vessels provide important information about their arrangement and connection to the aortic arch. Bilateral ductus arteriosus is often a marker of complex vascular anomalies, which are frequently associated with genetic syndromes. Show less

Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. This study establishes an estrogen receptor (ERα)/MAPK (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 extracellular signal-regulated kinase (ERK)5 and MAP-ERK kinase (MEK)5, it was revealed that hormone activation of ERα determined the subcellular localization of ERK5, which functions as a coregulator of ERα-dependent gene transcription. Notably, ERK5 acted in concert with the actin remodeling protein, CFL1, and upon hormone exposure, both localized to active nuclear transcriptional hubs as verified by immunofluorescence and proximity ligation assays. Both ERK5 and CFL1 facilitated PAF1 recruitment to the RNA Pol II complex and both were required for regulation of gene transcription. In contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely contributing to the generally poorer prognosis of patients with ERα-negative breast cancer. Thus, this study uncovers the dynamic interplay of nuclear receptor-mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness. Identification of the ER/ERK5/CFL1 axis suggests new prognostic biomarkers and novel therapeutic avenues to moderate cancer aggressiveness. Show less