|dc.description.abstract||Abstract: Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied.
To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene
(3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with
muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also
observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma.
Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by
using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked
loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq
showed a deregulated gene expression pattern for key biological processes such as angiogenesis,
migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among
the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5
as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important
determinant of sarcoma biology that should be further studied in human pathology.||spa