Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness

Abstract

AbstractMicronuclei (MN) can arise from many causes, including the breakage of aberrant cytokinetic chromatin bridge. The frequent observation of MN in tumors raises the specter that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we test the hypothesis that the presence of micronuclei could induce specific phenotypic and functional changes to the cell and lead to increased cancer invasive potential. With a variety of imaging and molecular methodsin vitroand in clinical samples from prostate cancer (PCa) patients, we show that chromosome bridge resolution can lead to EMD accumulation and formation of EMD-rich MN. Such structure is negative for Lamin A/C and positive for LBR and Sec6β. It can cause EMD pauperization from NE affecting migratory and invasive properties of a cell and can be translated to PCa patient’s poor prognosis.