The transcription factor SOX11 in liposarcomas, synovial sarcomas and malignant peripheral nerve sheath tumors: functional role and influence on the transcriptional network

• Applicant: Professor Dr. Kai Breuhahn, since 1/2022
• Subject Area: Pathology ; Hematology, Oncology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 328544030

The aim of the submitted proposal is the functional evaluation of the transcription factor SOX11 in different liposarcoma (LS) types (well-differentiated LS, dedifferentiated LS, myxoide LS, and pleomorphic LS), in synovial sarcomas (SySa), and malignant peripheral nerve sheath tumors (MPNST). The four aims are autonomous of each other and allow the identification of sarcoma type-specific and general functions of SOX11 with effective input of resources: Aim 1: Functional evaluation of SOX11 in the different LS types, MPNST, and SySa in vitro (viability, proliferation, migration, invasion, apoptosis, interaction of SOX11 with relevant chemotherapeutics and small molecules) with in vivo translation of phenotypes mediated by SOX11. The SOX11-driven transcriptional network will by identified for the different sarcoma subtypes by using RNA- and ChIP-Seq analyses with subsequent integration of the data sets. SOX11 target genes and miRNAs as well as signaling pathways will be analyzed in detail with regard to the different sarcoma types. Aim 2: In parallel, the growth inhibitory effects of SOX1 observed in the MLS cell line MLS-1765 will be explored in regard to a putative direct or indirect interaction between SOX11 and p53. Aim 3: Finally, the role of SOX11 during adipogenesis using LS cell lines and during the FUS-DDIT3- and SS18-SSX-driven transformation of mesenchymal stem cells will be identified. Aim 4: In view to a diagnostic benefit of SOX11, the aim is to detect exosomal SOX11 mRNA in sarcoma cell lines and in blood serum of patients with MLS and SySa.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Marcus Renner, until 1/2022