TBX3 is overexpressed in diverse sarcoma subtypes and functions as an oncoprotein in chondrosarcomas while acting as a tumour suppressor in fibrosarcomas.
Does TBX3 knockdown or overexpression alter the oncogenic phenotype in sarcoma cell lines and mouse models?
TBX3 is overexpressed in diverse sarcoma subtypes and acts as either an oncogene or tumor suppressor depending on the cellular context.
Sarcomas represent a complex group of malignant neoplasms of mesenchymal origin and their heterogeneity poses a serious diagnostic and therapeutic challenge. There is therefore a need to elucidate the molecular mechanisms underpinning the pathogenesis of the more than 70 distinguishable sarcoma subtypes. The transcription factor TBX3, a critical developmental regulator, is overexpressed in several cancers of epithelial origin where it contributes to tumorigenesis by different molecular mechanisms. However, the status and role of TBX3 in sarcomas have not been reported. Here we show that a diverse subset of soft tissue and bone sarcoma cell lines and patient-derived sarcoma tissues express high levels of TBX3. We further explore the significance of this overexpression using a small interferring RNA approach and demonstrate that TBX3 promotes the migratory ability of chondrosarcoma, rhabdomyosarcoma and liposarcoma cells but inhibits fibrosarcoma cell migration. This suggested that TBX3 may play a key role in the development of different sarcoma subtypes by functioning as either an oncoprotein or as a brake to prevent tumour progression. To further explore this, TBX3 knockdown and overexpression cell culture models were established using chondrosarcoma and fibrosarcoma cells as representatives of each scenario, and the resulting cells were characterized with regard to key features of tumorigenesis. Results from in vitro and in vivo assays reveal that, while TBX3 promotes substrate-dependent and -independent cell proliferation, migration and tumour formation in chondrosarcoma cells, it discourages fibrosarcoma formation. Our findings provide novel evidence linking TBX3 to cancers of mesenchymal origin. Furthermore, we show that TBX3 may be a biomarker for the diagnosis of histologically dynamic sarcoma subtypes and that it impacts directly on their oncogenic phenotype. Indeed, we reveal that TBX3 may exhibit oncogene or tumour suppressor activity in sarcomas, which suggests that its role in cancer progression may rely on cellular context.
Willmer et al. (2016) studied Sarcoma. TBX3 knockdown and overexpression vs. Control (shCtrl or FLAG-Empty) was evaluated on Tumorigenesis (cell proliferation, migration, and tumour formation). TBX3 is overexpressed in diverse sarcoma subtypes and functions as an oncoprotein in chondrosarcomas while acting as a tumour suppressor in fibrosarcomas.