Searchable abstracts of presentations at key conferences in endocrinology

ea0077oc6.4 | Thyroid | SFEBES2021

AP-2 and Moesin Regulate the Internalisation of the Sodium-Iodide Symporter and Affect I125 Uptake in Thyroid Cancer Cells.

Thornton Caitlin , Brookes Kate , Alice Fletcher , Nieto Hannah , Zha Ling , Kocbiyik Merve , Read Martin , Smith Vicki , McCabe Chris

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...

ea0086op6.3 | Endocrine Cancer and Late Effects | SFEBES2022

Knockout mouse embryonic fibroblasts reveal a physiological role for the proto-oncogene PBF in cell adhesion and motility

Kocbiyik Merve , Manivannan Selvambigai , Brookes Katie , Zha Ling , Nieto Hannah R , Read Martin L , McCabe Christopher J , Smith Vicki E

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...

ea0077oc2.4 | Endocrine Cancer and Late Effects | SFEBES2021

PBF phosphorylation regulates cell motility of thyroid and breast cancer cells

Kocbiyik Merve , Alshahrani Mohammed , Poole Vikki L , Jeyanathan Sakaorna , Thornton Caitlin , Zha Ling , Brookes Katie , Nieto Hannah , Read Martin L , McCabe Chris J , Smith Vicki E

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...

ea0086oc2.2 | Endocrine Cancer and Late Effects | SFEBES2022

Promotion of thyroid cancer cell migration and invasion by the proto-oncogene PBF is mediated by FGD1 and N-WASP

Manivannan Selvambigai , Alshahrani Mohammed , Thornton Caitlin EM , Raja Saroop , Kocbiyik Merve , Zha Ling , Brookes Katie , Nieto Hannah R , Read Martin L , McCabe Christopher J , Smith Vicki E

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...

ea0086oc2.6 | Endocrine Cancer and Late Effects | SFEBES2022

Repurposing disulfiram as a therapeutic agent to enhance sodium iodide symporter activity in radioiodide therapy

Read Martin , Brookes Katie , Zha Ling , Kim Jana , Moolla Mehjabi , Kocbiyik Merve , Manivannan Selvambigai , Hoare Rachel , Kannappan Vinodh , Wang Weiguang , Sunassee Kavitha , Blower Philip , Nieto Hannah , Smith Vicki , McCabe Christopher

Background: New drug approaches are urgently needed that enhance radioiodide (RAI) uptake leading to efficient ablation of thyroid cancer, especially in RAI-refractory disease. We recently utilised high-throughput screening and identified FDA-approved compounds that induce sodium iodide symporter (NIS) function to enhance iodide uptake, including the proteasomal/ VCP inhibitor disulfiram. In vivo, disulfiram is rapidly metabolized to diethyldithiocarbamate (DDC), whic...