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...

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...

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...

By exploiting the canonical function of the sodium iodide symporter (NIS), ablative radioiodide therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodide due to decreased expression and/or plasma membrane localisation of NIS. Radioiodide therapy has been proposed as a viable treatment for breast cancer, but is hampered by low levels of NIS membrane localisation. Currently, the regulation of NIS trafficki...

Worldwide, ˜300,000 new cases of differentiated thyroid cancer are reported per annum and thyroid cancer now represents the most rapidly increasing cancer in the US and in the UK. In general terms, outcome is good (10-year survival >90%). However, up to 25% of patients develop local or regional recurrences, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver ...

By exploiting the canonical function of the sodium iodide symporter (NIS), ablative radioiodide therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodide due to decreased expression and/or plasma membrane localisation of NIS. Radioiodide therapy has been proposed as a viable treatment for breast cancer, but is hampered by low levels of NIS membrane localisation. Currently, the regulation of NIS trafficki...

Worldwide, ˜300,000 new cases of differentiated thyroid cancer are reported per annum and thyroid cancer now represents the most rapidly increasing cancer in the US and in the UK. In general terms, outcome is good (10-year survival >90%). However, up to 25% of patients develop local or regional recurrences, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver ...