Searchable abstracts of presentations at key conferences in endocrinology

ea0059p225 | Thyroid | SFEBES2018

Using lightsheet microscopy to explore the relationship between NIS and its functional interactors ARF4, VCP and PBF

Thornton Caitlin , Fletcher Alice , Brookes Katie , Alshahrani Mohammed , Read Martin , Boelaert Kristien , Smith Vicki , McCabe Chris

Effective treatment of differentiated thyroid cancer relies on a multifaceted approach often including administration of 131I to ablate residual cancer cells post-surgery. The success of this treatment hinges upon adequate uptake of iodide by malignant thyroid follicular cells. In a subset of patients, dedifferentiation of the carcinoma can result in aberrant expression and trafficking of the iodide transport protein, the sodium iodide symporter (NIS), resulting in ...

ea0077oc2.2 | Endocrine Cancer and Late Effects | SFEBES2021

An emerging role for proteostasis modulators targeting NIS activity to enhance radioiodide therapy in thyroid cancer

Read Martin , Brookes Katie , Thornton Caitlin , Nieto Hannah , Zha Ling , Fletcher Alice , Boelaert Kristien , Smith Vicki , McCabe Christopher

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...

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...

ea0059oc2.4 | The best of the best | SFEBES2018

Biochemical analysis of radioiodine uptake enhancement in endocrine cancer

Alshahrani Mohammed , Fletcher Alice , Thornton Caitlin , Brookes Kate , Nieto Hannah , Thompson Rebecca , Read Martin , Boelaert Kristien , McCabe Christopher , Smith Vicki

The most common form of endocrine cancer is differentiated thyroid cancer (DTC). Outcomes of DTC largely depend on radioiodine treatment, which is mediated the sodium-iodide symporter (NIS). However, many tumours exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transform...

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...

ea0065oc4.1 | Thyroid | SFEBES2019

A high-throughput yellow fluorescent protein (YFP) cell-based screen identifies autophagy modulators to increase the effectiveness of radioiodine therapy

Read Martin , Baker Katie , Fletcher Alice , Thornton Caitlin , Alshahrani Mohammed , Nieto Hannah , Khan Rashida , Webster Jamie , Haggie Peter , Verkman Alan , Alderwick Luke , Boelaert Kristien , Smith Vicki , McCabe Christopher

New targeted drug strategies are urgently needed to improve radioiodine uptake and efficiently ablate thyroid cancer cells thereby minimising the risk of recurrent disease. High-throughput screening (HTS) offers a promising approach to identify new candidate drugs that will induce sodium iodide symporter (NIS) function to promote iodide uptake. However, significant progress has been limited by a lack of thyroid cell-based assays amenable to HTS. Here, we constructed a thyroid ...

ea0065oc4.6 | Thyroid | SFEBES2019

Driver events in thyroid cancer recurrence

Nieto Hannah , Thornton Caitlin , Fletcher Alice , Menezes Albert Nobre de , Brookes Katie , Alshahrani Mohammed , Read Martin , Boelaert Kristien , Smith Vicki , Cazier Jean-Baptiste , Mehanna Hisham , McCabe Chris

Thyroid cancer is increasing in incidence worldwide. While outcomes are generally good, up to 25% of patients suffer recurrence, and this has a significant impact on their quality of life and life expectancy. We hypothesised that thyroid tumours which recur display a distinct pattern of driver events, present on initial histology. Controlled-access TCGA data on thyroid cancer were downloaded and whole exome sequencing data analysed. An analysis pipeline utilising Platypus, Ann...

ea0065op2.4 | Thyroid | SFEBES2019

The proto-oncogene PBF mediates Src modulation of radioiodine uptake

Alshahrani Mohammed , Fletcher Alice , Thornton Caitlin , Brookes Kate , Nieto Hannah , Thompson Rebecca , Raja Saroop , Read Martin , Boelaert Kristien , McCabe Christopher , Smith Vicki

Successful responses to radioiodine treatment in differentiated thyroid cancer ultimately depend on uptake via the sodium-iodide symporter (NIS). However, many tumors exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transforming gene-binding factor (PBF) is partially res...

ea0065p393 | Thyroid | SFEBES2019

Investigating the mechanism behind sodium-iodide symporter trafficking by the small GTPase ARF4

Thornton Caitlin EM , Fletcher Alice , Nieto Hannah , Brookes Kate , Alshahrani Mohammed , Read Martin , Boelaert Kristien , Stewart Grant S , Smith Vicki E , McCabe Chris

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...

ea0063oc9.3 | Thyroid 2 | ECE2019

Novel driver mutations in thyroid cancer recurrence

Nieto Hannah , Thornton Caitlin , Fletcher Alice , de Menezes Albert Nobre , Baker Kate , Alshahrani Mohammed , Read Martin , Boelaert Kristien , Smith Vicki , Baptiste Cazier Jean , Mehanna Hisham , McCabe Chris

The incidence of thyroid cancer is rapidly increasing worldwide. Whilst outcome in thyroid cancer is generally good, up to 25% of patients develop recurrence, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver events. Whole exome sequencing data were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatic analysis of data on N=43 patients whose tumours recurred was ...