Figure 7: Model of PHD3 function in the control of tumour growth.
From: PHD3 regulates EGFR internalization and signalling in tumours
PHD3 is induced by hypoxia to promote the recruitment of Eps15 and epsin1 and promote EGFR internalization, which leads to attenuation of EGFR signalling and function. Silencing of PHD3 expression during tumour progression (for example, by genetic deletion or epigenetic silencing) impairs Eps15 and epsin1 recruitment and EGFR internalization. As a consequence, EGFR is retained at the membrane, resulting in the acquisition of growth signal autonomy through hyperactivation of EGFR and thus increasing tumour resistance to the growth-inhibitory and pro-apoptotic effects of hypoxia.
