Endocrine Abstracts

The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is upregulated in multiple tumours including thyroid cancer. PBF overexpression mediates tumorigenic processes such as cell motility and accelerates thyroid cancer cell invasion. We have recently shown that both PBF phosphorylation at tyrosine 174 (Y174) and PBF endocytosis are required for PBF-stimulated thyroid and breast cancer cell migration and invasion. This prompted further investigation into a ph...

The proto-oncogene pituitary tumor transforming gene binding factor (PTTG1IP/PBF) is overexpressed in multiple tumours and associated with tumour progression. One of the tumourigenic processes that PBF can mediate is cell motility. PBF can induce cell invasion in both thyroid and breast cancer cell lines. However, in contrast to wild-type (WT) PBF, the Y174A PBF mutant was not able to induce the invasiveness of thyroid or breast cancer cells. The Y174 residue is highly phospho...

Thyroid tumor progression is dependent on cell motility, a highly complex process that involves the co-ordination of cell adhesion, actin dynamics and signal transduction. The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) is a transmembrane glycoprotein that is overexpressed in thyroid cancer and associated with a poorer prognosis. PBF significantly promotes thyroid cancer cell migration and invasion through phosphorylation at PBF-Y174 by...

Background: The sodium/iodide symporter (NIS) frequently shows diminished targeting to the plasma membrane (PM) in differentiated thyroid cancer, resulting in suboptimal radioiodine treatment and poor prognosis. However, the mechanisms which govern the endocytosis of NIS away from the PM – its sole site of transport activity – are ill-defined, and may be of direct therapeutic potential. We previously showed that the proto-oncogene PBF binds NIS and enhances its inter...

Dysfunctional regulation of sodium-iodide symporter (NIS) trafficking can result in ineffective radioiodide uptake in patients with differentiated thyroid cancer. Understanding the trafficking pathways of this key protein can be used to optimise radioiodide therapy. Recently, we identified via HiLo microscopy that the protein ADP-ribosylation Factor 4 (ARF4) helps shuttle NIS to the plasma membrane. To understand how ARF4 interacts with NIS mechanistically, we utilised advance...

PTTG is a multifunctional proto-oncogene, overexpressed in thyroid, pituitary and other endocrine cancers. PTTG is also implicated in the pathogenesis of head and neck cancer, where high PTTG expression independently correlates with advanced tumour stage and reduced disease-free survival. Recently, abrogation of residue threonine-60 (T60) has been associated with altered PTTG half-life, chromosomal instability and cell invasion. We therefore generated a phospho-specific antibo...

The ability of the thyroid to accumulate iodide via the sodium-iodide symporter (NIS) can be utilised to successfully treat the majority of thyroid cancers with radioiodide. However, approximately 25% of thyroid cancers lose this functional NIS activity and become unresponsive to radioiodide therapy, resulting in a poorer prognosis. Our knowledge of NIS regulation is limited, but as dimerisation of NIS has been proposed, we sought to investigate NIS dimerisation and its impact...

The ability of the thyroid to accumulate iodide via the sodium-iodide symporter (NIS) can be utilised to successfully treat the majority of thyroid cancers with radioiodide. However, approximately 25% of thyroid cancers lose this functional NIS activity and become unresponsive to radioiodide therapy, resulting in a poorer prognosis. Our knowledge of NIS regulation is limited, but as dimerisation of NIS has been proposed, we sought to investigate NIS dimerisation and its impact...