Abstract:
:Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.
journal_name
Oncogenejournal_title
Oncogeneauthors
Franzetti GA,Laud-Duval K,van der Ent W,Brisac A,Irondelle M,Aubert S,Dirksen U,Bouvier C,de Pinieux G,Snaar-Jagalska E,Chavrier P,Delattre Odoi
10.1038/onc.2016.498subject
Has Abstractpub_date
2017-06-22 00:00:00pages
3505-3514issue
25eissn
0950-9232issn
1476-5594pii
onc2016498journal_volume
36pub_type
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