Overexpression of the T-Box Transcription Factor TBX3 as an early marker of Sarcomas – Associate Professor Sharon Prince
Associate Professor Sharon Prince
Department of Human Biology, Faculty of Health Sciences, University of Cape Town
Overexpression of the T-Box Transcription Factor TBX3 as an early marker of Sarcomas.
According to the World Health Organisation, the annual number of new cancer cases is likely to increase from 11.3 million in 2007 to 15.5 million in 2030, with 70% of these cases occurring in developing countries. Many cancers can be treated or at least managed effectively if detected early. At a molecular level, the initiation of cancer can be characterised, in part, by the deregulation of proteins called transcription factors, which function by turning on tumour promoting genes and/or switching off tumour suppressor genes. TBX3 is a transcription factor that plays a very important role during embryonic development of many species. For example, it is involved in the development of the limbs, heart and mammary glands. In humans, mutations in the TBX3 gene that result in decreased levels of functional TBX3 protein results in ulnar-mammary syndrome and individuals suffering from this syndrome have abnormal limbs with missing fingers, underdeveloped breasts and in some cases heart defects. More recently, increased levels of functional TBX3 have been linked to a growing list of cancers including breast, liver, bladder, pancreatic, gastric and melanoma. Research in our laboratory has investigated the role of TBX3 in melanoma and breast cancer and we have shown that it is a key factor that drives tumour formation and the spreading of these cancers.
We also recently reported novel data showing that TBX3 levels are abnormally high in cancers that originate from soft tissues (fibrosarcomas, liposarcomas and rhabdomyosarcomas) and bones (Willmer et al., 2016). These cancers are called sarcomas which are highly aggressive cancers that affect young children and adolescents and their clinical management is severely limited due to their heterogeneity, aggressive nature and their insensitivity to current treatments. It is generally accepted that this burden can be reduced if we had adequate diagnostic markers. Of special interest to us is our observation that the increase in TBX3 levels occurs at an early stage of fibrosarcoma development which suggests that it may be used as an early marker of sarcomas in general. If this were the case then TBX3 can be used as a clinical indicator to diagnose sarcomas early and therefore improve the survival of patients with this disease. To confirm this and to identify other proteins that can be used in combination with TBX3 in the diagnosis of sarcomas we propose to examine the status of TBX3 mRNA and protein levels in a number of patient derived sarcomas at different stages of tumour progression and to identify protein(s) that are responsible for upregulating TBX3 levels in sarcomas as well as to identify proteins that co-operate with TBX3 to drive sarcoma formation. Results from this study may lead to the discovery of additional biomarkers that can be used in conjunction with TBX3 for more accurate early detection and diagnosis of sarcomas.