Endocrine Abstracts

Prostate cancer (PC), the most commonly diagnosed malignancy among men, is a complex and heterogeneous disease that is highly influenced by the endocrine environment, which makes difficult the identification of novel therapeutic biomarkers to treat this pathology. Somatostatin (SST) is a pleiotropic neuropeptide that exerts its multiple biological functions, including tumor cell regulation, through a family of receptors (named sst1-5). Particularly, in this study we have found...

Neuroendocrine neoplasms (NENs) are a highly heterogeneous group of tumors that arise from the diffuse neuroendocrine system and whose incidence has increased over the last years. Among them, pancreatic NENs (PanNENs) are relatively common and one of the most studied NENs. PanNENs are characterized by a low number of mutations, with some genes frequently mutated, such as MEN1, ATRX/DAXX, and mTOR signaling pathway genes. Despite genomics, transcripto...

Lung carcinoids are slow-proliferating neuroendocrine neoplasms commonly showing low mutational burden but a high heterogeneity and difficult clinical management. Despite valuable advances in their molecular characterization, some aspects remain still unknown. Recent studies have shown that alternative splicing is severely dysregulated in lung carcinoids, where it could promote tumoral features. In contrast, the role of some molecular systems closely related to splicing and ot...

Neuroendocrine tumors (NETs) and carcinomas (NECs) are a heterogeneous group of malignances whose incidence is increasing worldwide. First-line approach is represented by surgery, whereas an effective pharmacological treatment for disseminated and relapsing disease is still needed. Somatostatin (SS) receptors (SSTs) constitute the main suitable pharmacological targets for NETs therapy with SS analogs (SSAs). Nevertheless, a large proportion of NETs and most NECs, are unrespons...

Metabolic syndrome (MetS) and type-2 diabetes (T2D) development is critically affected by the loss of phenotypic flexibility (i.e. the difficulty to cope with stressors to maintain metabolic homeostasis). Thus, it is essential to identify key modifiers of phenotypic plasticity that define individual susceptibility to develop T2D. Particularly, there is emerging evidence that alternative mRNA splicing is dysregulated under adverse metabolic-conditions, such as T2D, in several t...

Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of several endocrine secretions. In particular, SST and CORT are two primary negative regulators of GH secretion. Consequently, SST or CORT knockout (KO) mice exhibit elevated GH levels; however, this does not lead to increased IGF-I levels or somatic growth, which has been suggested that could be due to a compensatory mechanism between both peptides. In order to test this...

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine neoplasms (NENs) that arise in the adrenal medulla and paraganglia, respectively. As occurs in the rest of NENs, PPGLs commonly present a high density of somatostatin receptors (SSTs) on their membrane. However, unlike in most NENs, somatostatin analogues (SSAs) do not represent a suitable therapeutic target in PPGLs, and the mechanisms underlying this mismatch are still unclear. In this study, we aim to iden...

Pheochromocytomas and paragangliomas (PPGL) are infrequent neuroendocrine neoplasms, which develop metastases or aggressive behaviour in 25 % patients. They can be classified into three clusters according to their molecular features; nevertheless, these differences may not stratify patients according to their prognosis. The dysregulation of the splicing process has emerged as a novel feature shared by most cancers, which is associated with an aggressive phenotype in several tu...

There is increasing evidence that alterations in alternative splicing can be linked to key tumor features in cancer. Dysregulations in the splicing machinery constitute the underlying cause in many of these alterations and, consequently, splicing and its control are emerging as a novel and transversal cancer hallmark, due to its association with different dysfunctions of tumor cells. In line with this, we discovered the existence of aberrantly spliced variants of somatostatin ...

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...