Endocrine Abstracts

Dysregulation of the splicing machinery is emerging as a novel cancer hallmark due to its association with multiple dysfunctions in tumor cells. An inappropriate function of the components of this machinery (spliceosome) could be primarily linked with the generation of tumor-associated aberrant splicing variants. In line with this, we have previously reported that overexpression of aberrantly spliced variants of somatostatin receptor 5 (sst5TMD4) and ghrelin (In1-ghrelin) is d...

: Hepatic steatosis is a common obesity-associated pathology characterized by the accumulation of fat within the liver, which can progress to liver fibrosis, cirrhosis and ultimately lead to hepatocellular carcinoma. Remarkably, obesity and cancer course with a profound dysregulation of the genetic expression patterns and, particularly, with the aberrant expression of splicing variants that could contribute to the aggressiveness and comorbidities of these pathologies. Since th...

: Prostate cancer (PCa) is the most common cancer among men in developed countries. Unfortunately, the heterogeneity of this malignancy hinders the finding of new biomarkers and therapeutic tools. A potential factor contributing to PCa is alternative splicing, which can generate the appearance of oncogenic variants involved in PCa aggressiveness. Thus, we hypothesized that the alteration of the splicing machinery (spliceosome components and splicing factors (SFs)) could be ass...

Prevalence of metabolic syndrome (MetS) and type-2 Diabetes (T2D) is growing dramatically worldwide. Loss of phenotypic flexibility, i.e. the difficulty to cope with different stressors to maintain metabolic homeostasis, contributes critically to the development of MetS/T2DM. Thus, it is essential to identify the key modifiers of phenotypic plasticity that define an individual’s susceptibility to develop T2DM. In this scenario, emerging evidence indicates that, under adve...

Somatostatin is a pleiotropic neuropeptide that governs multiple biological targets, including tumor cell function, through a family of G protein-coupled receptors with 7-transmembrane domains (TMD), named sst1-5. However, we recently discovered sst5TMD4, an aberrantly spliced, truncated (only 4-TMDs) sst5-variant displaying unique molecular/functional features. sst5TM4 is overexpressed in various endocrine-related tumors exacerbating their malignant characteristics. Here, we ...

Obesity, a disease that is growing at epidemic proportions worldwide, is caused by a combination of genetic and lifestyle factors. One of the most common pathologies associated with obesity is hepatic steatosis, an accumulation of fat within the liver that can progress to liver fibrosis, cirrhosis, and ultimately lead to hepatocellular carcinoma. There is emerging evidence that alternative mRNA splicing, the key mechanism providing transcript and protein diversity, is dysregul...

Dietary fat influences systemic inflammatory status, which, in turn, determines the progression of age-associated diseases. Peripheral blood mononuclear cells (PBMCs) comprise a subset of white blood cells placed at the crossroad between diet and inflammation, in that they play a key role in the immune/inflammatory system and their gene expression pattern is influenced by diet. Since the somatostatin (SST), cortistatin (CORT) and ghrelin systems have been shown to modulate the...

Metformin has recently emerged as a potential therapeutic tool for different tumour pathologies, including prostate cancer (PCa)1, one of the leading causes of cancer-deaths in men worldwide. However, the molecular mechanisms underlying the antitumor effects of metformin in PCa are not fully elucidated. In this context, previous reports have suggested a relationship between metformin and the process of alternative splicing in some cell-types. Nevertheless, the poten...

omatostatin, originally isolated from ovine hypothalami in 1973, and cortistatin, identified a decade ago in amphibians and then in human and rodents, are two highly related peptides thought to derive from a common ancestor gene. Owing to their high structural homology, both peptides bind with similar affinity to the five so-called somatostatin receptors (sst1-sst5), and exert virtually undistinguishable effects on several physiological targets, including inhibition of endocri...

Prostate cancer (PCa) is the most common tumor pathology in men worldwide. The medical treatments currently used as first-line therapy after surgery are anti-androgens like abiraterone or enzalutamide, which, unfortunately, fail to stop the disease in a high percentage of cases, resulting in progression towards aggressive castration-resistant PCa. Therefore, new therapeutic tools to manage PCa are urgently needed. Biguanides and statins, two types of drugs commonly used in met...