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 ...

ea0031oc2.3 | Steroids and thyroid | SFEBES2013

A bi-transgenic murine model of PTTG and PBF overexpression in the thyroid gland

Fong Jim , Read Martin , Ryan Gavin , Lewy Greg , Smith Vicki , Boelaert Kristien , Franklyn Jayne , McCabe Chris

Whilst the majority of differentiated thyroid cancers (DTC) have oncogenic mutations, a significant minority may be driven by the overexpression of proto-oncogenes. PTTG and PBF are proto-oncogenes which are induced in DTC, elicit tumours in xenograft models and interact in vitro, where PBF shuttles PTTG into the nucleus. However, the relative contributions of each gene to DTC has not been delineated. Here, we constructed a bi-transgenic murine model over-expressing b...

ea0015p174 | Endocrine tumours and neoplasia | SFEBES2008

A new pathway in the induction of breast cancer

Watkins Rachel , Smith Vicki , Read Martin , Vasilopoulou Elisavet , James Sally , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...

ea0015p178 | Endocrine tumours and neoplasia | SFEBES2008

A novel mechanism of NIS repression in differentiated thyroid cancer

Smith Vicki , Read Martin , Watkins Rachel , Turnell Andrew , James Sally , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most differentiated thyroid tumours exhibit reduced iodide uptake, however, and the mechanisms accounting for this remain poorly understood. Pituitary tumor transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We recently reported that PTTG and its binding factor PBF, also a potent transfo...

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...

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...

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...

ea0038oc5.1 | Thyroid and parathyroid | SFEBES2015

Functional consequences of germline mutations in a novel non-RET medullary thyroid cancer susceptibility gene

Read Martin , Smith Joel , Smith Vicki , Bosseboeuf Emy , Wake Naomi , Watkinson John , Wallis Yvonne , Maher Eamonn , McCabe Christopher , Woodward Emma

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...

ea0038oc6.5 | Advances in reproduction and signalling | SFEBES2015

Pituitary tumor transforming gene binding factor (PBF): a novel modulator of iodide uptake and target for Src phosphorylation in breast cancer

Poole Vikki , Fletcher Alice , Modasia Bhavika , Sharma Neil , Thompson Rebecca , Imruetaicharoenchoke Waraporn , Read Martin , Boelaert Kristien , Smith Vicki , McCabe Christopher

Although the sodium iodide symporter (NIS) is expressed in 70–80% of breast cancers, only 20–30% is located at the plasma membrane (PM) and therefore functional. Previous work in thyroid cells leads demonstrated that PBF redistributes NIS from the PM into intracellular vesicles, potently reducing radioiodide uptake. We therefore examined whether increased membranous NIS could facilitate radioiodide therapy for breast cancer. Immunofluorescent microscopy revealed co-l...