Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0077oc2.3 | Endocrine Cancer and Late Effects | SFEBES2021

A novel in vivo platform for studying tumour vascularization and endocrine responses

Lopes Tatiana , Prague Julia , Salem Victoria , Owen Bryn

Background: Tumour growth is critically dependent on blood perfusion, its source of oxygen and nutrients. Therefore, tumour vascularization has become an attractive target for the treatment of many cancers types. The study of endocrine-responsive tumours, in particular, needs improved platforms to screen drugs targeting vascularization that have better resolution and that do not compromise on inter-individual variability.Aim: Hence, we’ve set out to...

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...

ea0077oc2.5 | Endocrine Cancer and Late Effects | SFEBES2021

A novel MiR-346-Directed DNA damage mechanism is regulated by its interaction with long non-coding RNA, NORAD, in prostate cancer

Fletcher Claire , Orafidiya Folake , Deng Lin , Yuan Wei , Lorentzen Marc , Cyran Oliwia , Varela-Carver Anabel , Constantin Theodora , Dobbs Felix , Figueiredo Ines , Gurel Bora , Parkes Eileen , Bogdan Denisa , Pereira Ronnie , Zhao Shuang (George) , Neeb Antje , Issa Fadi , Hester Joanna , Kudo Hiromi , Liu Yang , Philippou Yiannis , Bristow Robert , Knudsen Karen , Bryant Richard , Feng Felix , Reed Simon , Mills Ian , de Bono Johann , Bevan Charlotte

MiR-346 is an Androgen Receptor (AR)-activating miR that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). MiR-346 induces rapid and extensive DNA damage in PC cells through chromatin association, activation of transcription, R-loop formation and DNA replication stress, leading to checkpoint activation and cell cycle arrest. MiR-346 interacts with lncRNA, NORAD, in PC cells, which functions to maintain mitosis, DDR, and chromosomal integrity...

ea0077oc2.6 | Endocrine Cancer and Late Effects | SFEBES2021

Transcriptomic analysis of succinate dehydrogenase subunit deleted cells to identify molecular mechanisms underlying the increased metastatic potential of SDHB-deficient tumours

Salsbury Grace , Hall Charlotte , Lim Eugenie , Read Jordan , Akker Scott , Chapple Paul

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

ea0077oc3.1 | Metabolism, Obesity and Diabetes | SFEBES2021

The serotonin transporter SLC6A4 protects human brown adipose tissue from serotonin-mediated suppression of thermogenesis.

Choong Kwok T’ng , Suchacki Karla , Ramage Lynne , Kelman Alexandra , McNeill Ben , Rodney Stewart , Keegan Matthew , Gray Calum , Manning Jonathan , MacNaught Gillian , Fletcher Alison , Simpson Joanna , Carter Roderick , Morton Nicholas , Homer Natalie , van Beek Edwin , Wakelin Sonia , Stimson Roland

The recent discovery of brown adipose tissue (BAT) in adult humans, which generates heat to maintain body temperature in a cold environment, offers an exciting new strategy to treat obesity and metabolic disease, but our knowledge of human BAT activation is limited. To identify novel pathways regulating human BAT, we undertook RNA sequencing of human brown and white adipocytes. The gene SLC6A4 (encoding the serotonin transporter SERT) was one of the most highly differ...

ea0077oc3.2 | Metabolism, Obesity and Diabetes | SFEBES2021

Comparing the transcriptional landscape between lean and obese mice within the small intestinal segments

Jacobs Margot , West Jason , Rajagopalan Harith , Bewick Gavin

Background: Obesity is a complex metabolic disease characterised by excess adipose tissue, that increases the risk of comorbidities such as type II diabetes. Interventions that rearrange the gut architecture or exclude nutrients from the duodenum promote immediate and long-term anti-diabetic effects, placing the gut front and centre in obesity and diabetes pathology and treatment. Currently, little is known about the pathological changes which occur in the small intestine (SI)...

ea0077oc3.3 | Metabolism, Obesity and Diabetes | SFEBES2021

Sex-specific risk of obesity and cardiometabolic disease in low- and middle-income countries (LMICs): a meta-analysis in 681929 individuals

Melson Eka , Rocha Thais , Zamora Javier , Fernandez-Felix Borja M , Sobhy Soha , Betran Ana Pilar , Arlt Wiebke , Thangaratinam Shakila

Introduction: Obesity is a global health challenge with more than 60% of the world´s population with obesity living in LMICs. Studies have demonstrated that women are more affected by obesity than men. However, the risk of obesity and obesity-related cardiometabolic diseases in women in LMICs have not been documented. The aims of this meta-analysis are: to evaluate the risk of obesity and obesity-related cardiometabolic disease in women compared to men in LMICs and to eva...

ea0077oc3.4 | Metabolism, Obesity and Diabetes | SFEBES2021

Hepatic choline deficiency underpins amelioration of visceral obesity and diabetes in ectonucleotide pyrophosphatase (Enpp)-6–/– mice

Wang Rongling , Schraut Katharina , Carter Roderick , Kentistou Katherine , Wilson James , Michailidou Zoi , Webster Scott , Morton Nicholas

The global prevalence of obesity continues to rise, creating a growing need for new effective medicines. Selective targeting of visceral obesity (fat around the internal organs) would be particularly advantageous because it carries a greater risk for cardiometabolic diseases. The ectonucleotide pyrophosphatase (ENPP) enzyme family participates in several pathological conditions including diabetes (ENPP1, and ENPP2, also known as autotaxin) and vascular dysfunction (ENPP3-4). O...

ea0077oc3.5 | Metabolism, Obesity and Diabetes | SFEBES2021

Microbial tryptophan metabolites modulate L-cell induced GLP-1 secretion to improve glucose homeostasis

Phuah Phyllis , Cheng Sijing , Norton Mariana , Roberts Anna , Otsubo Emile , Gribble Fiona , Reimann Frank , Hanyaloglu Aylin , Owen Bryn , Murphy Kevin

Growing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Gut microbial dysbiosis occurs in obesity, while high-fibre and high-protein diets, which improve glucose tolerance and induce weight loss, are associated with the generation of microbial metabolites. Understanding how the gut responds to microbial metabolites may identify mechanisms that induce satiety and improve glucoregulation, revealing novel therapeutic targets. Indole is generated f...