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