c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells
Ander Abarrategi
Stefano Gambera
Arantzazu Alfranca
Miguel A Rodriguez-Milla
Raquel Perez-Tavarez
Kevin Rouault-Pierre
Alexander Waclawiczek
Probir Chakravarty
Francisca Mulero
César Trigueros
Samuel Navarro
Dominique Bonnet
Javier García-Castro
10779/crick.12490433.v1
https://crick.figshare.com/articles/journal_contribution/c-Fos_induces_chondrogenic_tumor_formation_in_immortalized_human_mesenchymal_progenitor_cells/12490433
Mesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs expressing c-Fos generated tumors harboring a chondrogenic phenotype and morphology. Thus, here we show that c-Fos protein has a key role in sarcomas and that c-Fos expression in immortalized MPCs yields cell transformation and chondrogenic tumor formation.
2020-06-25 15:12:13
Animals
Carcinogenesis
Cell Line
Cell Transformation, Neoplastic
Gene Expression Regulation, Neoplastic
Genes, fos
Humans
Mesenchymal Stem Cells
Mice
Mice, Inbred NOD
Mice, SCID
Proto-Oncogene Proteins c-fos
Sarcoma
Bonnet FC001045
CB
BRF-ack
FC-ack
HP-ack
CS-ack
0601 Biochemistry and Cell Biology
0299 Other Physical Sciences