Figure 5. A model depicting the crosstalk between p63 and the IGF system. While the tumour suppressive TAp63 isoforms negatively control Igf1r transcription, the oncogenic ΔNp63 variants induce and repress the expression of the Irs1 and Igfbp3 genes, respectively. In HNSCC cells overexpressing ΔNp63, the transcription of Igf1r would be stimulated as a result of the unbalanced ratio between the TA/ΔN p63 proteins. Aberrant accumulation of IGF1R and its docking protein IRS1 would enhance signalling activation in response to receptor stimulation. On the other hand, reduced expression levels of Igfbp3 would increase the availability of circulating IGF1 that could further potentiate receptor activation.