title: Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells.
abstract: Soft tissue sarcomas with complex genomics are very heterogeneous tumors lacking simple prognosis markers or targeted therapies. Overexpression of a subset of mitotic genes from a signature called CINSARC is of bad prognosis, but the significance of this signature remains elusive. Here we precisely measure the cell cycle and mitosis duration of sarcoma cell lines and we found that the mitotic gene products overexpression does not reflect variation in the time spent during mitosis or G2/M. We also found that the CINSARC cell lines, we studied, are composed of a mixture of aneuploid, diploid, and tetraploid cells that are highly motile in vitro. After sorting diploid and tetraploid cells, we showed that the tetraploid cell clones do not possess a proliferative advantage, but are strikingly more motile and invasive than their diploid counterparts. This is correlated with higher levels of mitotic proteins overexpression. Owing that mitotic proteins are almost systematically degraded at the end of mitosis, we propose that it is the abnormal activity of the mitotic proteins during interphase that boosts the sarcoma cells migratory properties by affecting their cytoskeleton. To test this hypothesis, we designed a screen for mitotic or cytoskeleton protein inhibitors affecting the sarcoma cell migration potential independently of cytotoxic activities. We found that inhibition of several mitotic kinases drastically impairs the CINSARC cell invasive and migratory properties. This finding could provide a handle by which to selectively inhibit the most invasive cells.
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jemaà
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Samer
authors.initials: S
authors.lastname: Abdallah
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Lledo
authors.affiliation: INSERM U1218, Bergonié Cancer Institute, F-33076 Bordeaux, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Perrot
authors.affiliation: INSERM U1218, Bergonié Cancer Institute, F-33076 Bordeaux, France.
authors.forename: Tom
authors.initials: T
authors.lastname: Lesluyes
authors.affiliation: U1194 INSERM, IRCM, 34298 Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Teyssier
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roux
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: van Dijk
authors.affiliation: INSERM U1218, Bergonié Cancer Institute, F-33076 Bordeaux, France.|Department of Pathology, Bergonié Cancer Institute, F-33076 Bordeaux, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Chibon
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Abrieu
authors.affiliation: Universités de Montpellier, 34293 Montpellier, France.|CRBM, CNRS, UMR 5237, 34293 Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morin
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D018740:Genetic Heterogeneity; D006801:Humans; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*; D057891:Tetraploidy
chemical_list: D004273:DNA, Neoplasm
keywords: CINSARC; diploid/tetraploid; mitosis; motility; sarcoma