biostudies-literatureCasalino LWorldwide Cancer Research1878-90https://www.ebi.ac.uk/biostudies/studies/S-EPMC1847654biostudies-literatureUnknown26(7)Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin The EMBO journalFra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.PMC184765402-0347Yaniv MWeitzman JBVerde PCasalino LBakiri LTalotta FFusco AfalseFra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin 2007-01-01T00:00:00Z2007 Apr2026-03-16T16:42:59.07Z2019-03-27T02:03:42ZS-EPMC18476541734765310.1038/sj.emboj.7601617