Role and regulation of TBX2 and TBX3

Thesis

The T-box family of transcription factors plays a crucial role during embryonic development, especially in heart and limb formation. In the adult organism, two members of the family, TBX2 and TBX3, have been found to be overexpressed in several types of cancer associating them with tumour biology. However, little is known about their regulatory targets and subsequent function aside from their well-described role during development, that would give indications of their overall contribution to tumourigenesis. Here, an agnostic, genome-wide approach is chosen to reveal novel TBX2 and TBX3 regulated target genes in a human melanoma cell line, shedding further light on their regulatory activity. Furthermore, the regulation of the two T-box factors themselves by growth regulating pathways, dysregulated in cancer, is assessed. Both T-box factors are proposed to be involved in cancer homoeostasis, a process balancing nutrient supply and demand within the cancer cell to facilitate long-term proliferation without depletion of nutrients. Moreover, TBX2 and TBX3 are demonstrated to be regulated by the PI3K pathway mediated by PAX3, and that this regulation is implicated in the bypass of oncogene induced senescence.

Authors: Schmidt, J

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: cancer