Endocrine Abstracts

Introduction: New therapeutic strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. We recently utilised high throughput screening and identified FDA-approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. Categorisation revealed a high proportion of drugs that modulate proteostasis, with 6 of the top 15 targeting activity of...

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

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...

Background: Evidence suggests that pancreatic stellate cells (PSCs) are present in intra-/peri-islets in type 2 diabetes mellitus (T2DM). We isolated stellate cell from islets (ISC) of Goto-Kakizaki (GK) rats. Given these cells are intra-islets, which possibly affect the biological behavior of β-cell. This study was designed to determine the effects of ISC isolated from fibrotic islets of GK rats on β-cell function and survival.Methods: ISC was...

The progression of thyroid cancer is dependent on cell motility, a highly complex process that involves the co-ordination of multiple signalling pathways, cell adhesion, and actin dynamics. The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) potently stimulates thyroid cancer cell migration and invasion via PBF phosphorylation by Src kinase at residue Y174. Recent phosphoproteomic and RNA-Seq analyses revealed that upregulation of PBF in Nt...

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...

Introduction: New drug approaches are urgently required to improve radioiodide (RAI) uptake for efficient ablation of thyroid cancer cells in RAI-refractory disease. Employing high-throughput screening of FDA-approved compounds we recently identified drugs capable of robust induction of sodium iodide symporter (NIS) activity to promote RAI uptake1. In particular, a leading drug candidate – the well-established anti-alcoholism drug disulfiram (DSF) – had no...

Background: Diminished sodium iodide symporter (NIS) activity at the plasma membrane (PM) is frequently associated with suboptimal radioiodide (RAI) uptake and poor prognosis in differentiated thyroid cancer (DTC). Endocytosis is a key determinant of symporter activity, with our recent study demonstrating specific interaction of NIS with Adaptor Protein 2 (AP2) – a central player in endocytosis. Here, our objective was to determine whether NIS endocytosis...