A potential new role for the proto-oncogene PBF in endocrine cancer as a regulator of endothelial cells and angiogenesis

The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) has been implicated in multiple malignancies, including thyroid cancer, where PBF overexpression is associated with tumour progression and poorer prognosis. PBF promotes several tumourigenic processes such as cell migration and invasion and, although its primary function remains unclear, a physiological role for PBF in cell motility has recently been identified. PBF is ubiquitously expressed and whole genome transcriptomics studies in normal tissue suggest that the highest PBF expression is within blood vessels. Additionally, single cell transcriptomics data from numerous tissues including ovary, lung, liver and testes show that PBF expression is highest in endothelial cells within these tissues. However, the role of PBF in endothelial cells is completely uncharacterised. Given the critical role of angiogenesis in tumour growth and metastasis we hypothesised that PBF is a novel regulator of angiogenesis via induction of endothelial cell motility. Our preliminary studies have utilised siRNA-mediated PBF knockdown in human umbilical cord vein endothelial cells (HUVECs). Interestingly, we observed that reduced PBF expression increased endothelial cell tube formation in 2D Matrigel tube formation assays, suggesting that PBF may negatively regulate angiogenesis. This assay mimics multiple steps of angiogenesis including cell differentiation, reorganisation, and adhesion. However, intriguingly no difference was found in the rate of wound recovery when PBF levels were reduced in scratch wound assays indicating that PBF’s effects may be specific to responding to angiogenic stimuli response rather than general endothelial cell motility. These findings suggest that PBF could function as an angiogenic regulator in endothelial cells offering new insights into its role in vascular biology. This study represents the first steps towards uncovering the function of PBF in endothelial cells and may reveal a role for PBF in endothelial-driven processes linked to endocrine malignancy.