c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.

[liposarcoma]

Genomic amplification of the c-Jun proto-oncogene has been identified in ∼30 % of dedifferentiated liposarcomas (DDLPS ), but the functional contribution of c-Jun to the progression of DDLPS remains poorly understood . In previous work we showed that knock-down of c-Jun by RNA interference impaired the in vitro proliferation and in vivo growth of a DDLPS cell line (LP 6 ) with genomic amplification of the c-Jun locus . Here , we used gene expression analysis and functional studies in a broad panel of cell lines to further define the role of c-Jun in DDLPS and other soft tissue sarcomas . We show that c-Jun knock-down impairs transition through the G 1 phase of the cell cycle in multiple DDLPS cell lines . We also found that high levels of c-Jun expression are both necessary and sufficient to promote DDLPS cell migration and invasion in vitro . Our data suggest that high levels of c-Jun enhance motility in part by driving the expression of ENPP 2 /Autotaxin . c-Jun over-expression has minimal effects on in vitro proliferation but substantially enhances the in vivo growth of weakly tumourigenic DDLPS cell lines . Finally , we provide evidence that c-Jun genomic amplification and over-expression may have similar functional consequences in other types of soft tissue sarcoma . Our data suggest a model in which relatively low levels of c-Jun are sufficient for in vitro proliferation , but high levels of c-Jun enhance invasiveness and capacity for in vivo tumour growth . These observations provide an explanation for the selective advantage provided by c-Jun genomic amplification in vivo and suggest that sarcomas with elevated c-Jun levels are likely to have a particularly high malignant potential . Data from exon array and RNA-Seq experiments have been deposited in the GEO database (Accession No . GSE 57531 ).