Endocrine Abstracts

In thyroid cancer, a reduction in sodium iodide symporter (NIS) expression at the basolateral plasma membrane (PM) of thyrocytes decreases the efficacy of radioiodine imaging, ablative therapy and treatment of metastases. NIS overexpression in breast cancer has resulted in radioiodine being widely proposed as a novel therapeutic strategy. However, uptake is insufficient for tumour destruction. Augmenting NIS PM localisation represents an important therapeutic strategy for incr...

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...

Despite extensive genomic profiling a better understanding of the contributory factors that promote aggressive thyroid cancer is urgently needed. The proto-oncogenes PBF and PTTG have been implicated in thyroid cancer but there is a lack of information regarding their co-expression and specific roles in tumour progression. Separate studies have previously indicated that PBF and PTTG may disrupt pathways associated with the tumour suppressor p53 that are central to DNA-damage r...

PBF is a multifunctional proto-oncogene overexpressed in thyroid and other endocrine cancers. Previously we identified a functional interaction between PBF and the tumour suppressor p53 in well-differentiated thyroid cancer (WDTC). Here, we delineate the oncogenic mechanisms of PBF, along with its binding partner PTTG, in head and neck cancer (HNSCC), in which TP53 mutations (mutTP53) are common (>50%). HNSCC tissue revealed significant upregulation of PBF and PTTG mRNA (&...

Patients termed to have radioiodine-refractory differentiated thyroid cancer (RR-DTC) cannot accumulate sufficient radioiodine for a therapeutic response due to sodium iodide symporter (NIS) dysregulation via diminished expression and/or altered plasma membrane (PM) localisation. Currently, the regulation of NIS localisation remains poorly defined and despite protein-protein interactions being well-described to modulate trafficking events, the NIS interactome is limited. Previ...

Metastasis is a multistep process responsible for the majority of endocrine cancer deaths. Central to the ability of cells to move is the recruitment of actin fibres at the periphery of the cell by key proteins, especially the cortical actin binding protein cortactin. A full understanding of cortactin function is required in order to address metastatic cell activity within endocrine cancer. We used IP-MS to discover protein binding partners, and now identify the proto-oncogene...

Functional disruption of the tumour suppressor p53 has a critical role in promoting the development of most cancers. The proto-oncogenes PBF and PTTG1 both regulate p53 activity, but the relative contribution of each gene in influencing p53 function has not been delineated, especially in thyroid cancer where both proto-oncogenes are commonly overexpressed. To better understand the interplay between PTTG1, PBF and p53 in vivo, we examined p53 responses in primary thyrocytes cul...

Dysregulation of the processing and stability of mRNA encoding oncogenes or tumour suppressor proteins is a critical event in the pathogenesis of cancer. Previously, we demonstrated that the proto-oncogene PTTG-binding factor (PBF) is overexpressed in thyroid, pituitary and breast tumours. Critically, high PBF expression is associated with reduced disease-specific survival in thyroid cancer. However, the mechanisms responsible for regulating PBF expression are unknown. In this...

New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow...

PTTG1-binding factor (PBF) is an oestrogen-regulated proto-oncogene that is overexpressed in thyroid, breast and pituitary tumours. The precise role of PBF in tumourigenesis, however, has not been established, nor whether it is also an aetiological factor in non-endocrine cancer. In this study, we investigated PBF function in established colorectal cells and human tumours. Specific binding was evident between the tumour suppressor p53 and both endogenous and exogenous PBF in H...