Searchable abstracts of presentations at key conferences in endocrinology

ea0073s16.2 | Symposium 16: Splicing in endocrine-related cancers | ECE2021

Alternative splicing in breast cancer

Gahete Manuel D

The dysregulation of the splicing process has emerged as a novel hallmark of metabolic and tumor pathologies. Specifically, in breast cancer (BCa), which represents the most diagnosed cancer type among women worldwide, several oncogenic splicing variants have been reported to have a relevant pathophysiological role. This is the case of the splicing variants of HER2 gene, or the In1-ghrelin and SST5TMD4 isoforms, which exhibit oncogenic roles, increasing the malignancy, poor pr...

ea0040l17 | Truncated sst5 receptor variants in pituitary tumors and cancer | ESEBEC2016

Truncated sst5 receptor variants in pituitary tumors and cancer

Luque Raul M , Ibanez-Costa Alejandro , Gahete Manuel D , Castano Justo P

Endocrine-related cancers comprise a complex group of heterogeneous pathologies whose development and progression are profoundly conditioned by endocrine–metabolic deregulations. The well-known capacity of somatostatin (SST) to inhibit hormone secretion and cell proliferation in a wide variety of cell types, coupled to the ubiquitous expression of SST receptors (ssts) in normal and tumoral tissues, has led SST analogs (SSAs) to be extensively used in clinical practice for...

ea0032s11.1 | New mechanisms in SST analogue response | ECE2013

Functional relevance of truncated SST5 receptor variants

Luque Raul M , Ibanez-Costa Alejandro , Gahete Manuel D , Castano Justo P

Somatostatin (SST) and its related peptide cortistatin (CORT) exert multiple physiological actions through binding to a family of G-protein coupled receptors (sst1–sst5), commonly bearing seven transmembrane domains (TMDs). However, we have recently discovered that human, pig and rodent sst5 gene also generate, through non-canonical alternative splicing, novel truncated albeit functional sst5 variants that lack one o more TMDs. Our studies indicate that truncated sst5 var...

ea0022p655 | Neuroendocrinology and Pituitary (<emphasis role="italic">Generously supported by Novartis</emphasis>) | ECE2010

Kisspeptin selectively increases LH and GH, but not FSH, ACTH, PRL or TSH, release in primary pituitary cell cultures from a non-human primate (Papio anubis) via distinct signaling pathways and under influence of sex steroids

Cordoba-Chacon Jose , Luque Raul M , Gahete Manuel D , Kineman Rhonda D , Tena-Sempere Manuel , Castano Justo P

Kisspeptins (Kp), a peptide family encoded by Kiss1 gene, and their receptor Kiss1r were first identified by their anti-metastatic actions but have emerged as key regulators of the reproductive axis, where they integrate sexual, metabolic and seasonal cues to control hypothalamic GnRH release. Recent data indicates that some actions of Kps may be effected directly at the pituitary (PIT), since Kissr1 is expressed in the PIT and Kp stimulate luteinizing hormone (LH) secretion d...

ea0081oc10.5 | Oral Communications 10: Diabetes, Obesity, Metabolism and Nutrition 3 | ECE2022

Splicing dysregulation is associated with aggresive and metabolic-associated liver disease-derived hepatocellular carcinoma

Sanchez Natalia Herman , Lopez-Canovas Juan L , del Rio-Morenos Mercedes , Amado Victor , de la Mata Manuel , Rodriguez-Peralvarez Manuel , Luque Raul M , Gahete Manuel D

Metabolic-associated fatty liver disease (MAFLD) is a growing cause of hepatocellular carcinoma (HCC), but the molecular mechanisms associated with the pathological progression from MAFLD to HCC are still to be fully elucidated. The genomic and transcriptomic profile of HCC samples have been widely described; however, the proteomic landscape of MAFLD-derived HCC samples is mostly unknown. Here, we sought to perform the first quantitative proteomic analysis of HCC samples from ...

ea0049gp128 | Endocrine Tumours | ECE2017

Peptides derived from the sst5TMD4 extracellular domain increase malignancy of endocrine-related cancer cells

Gahete Manuel D , Rio-Moreno Mercedes del , Alors-Perez Emilia , de Souza Patricia Borges , Prados-Gonzalez Maria E , Castano Justo P , Luque Raul M

A growing number of studies suggest that extracellular fragments derived from plasma membrane receptors can play relevant functional roles in the development and progression of certain tumoral pathologies which might, therefore, serve as novel tools in the diagnostic and prognostic of such pathologies. In this scenario, the truncated somatostatin receptor sst5TMD4, which is overexpressed in various endocrine-related cancers (i.e. breast, prostate, neuroendocrine, liver and pit...

ea0049ep472 | Diabetes (to include epidemiology, pathophysiology) | ECE2017

Dysregulation of the splicing machinery could represent an early, predictive event in the development of type 2 diabetes

Alors-Perez Emilia , Rio-Moreno Mercedes del , Pedraza-Arevalo Sergio , Camargo Antonio , Delgado-Lista Javier , Lopez-Miranda Jose , Gahete Manuel D , Castano Justo P , Luque Raul M

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...

ea0041gp112 | Endocrine Tumours | ECE2016

Presence and clinical-histological correlates of ghrelin and somatostatin systems components in gastroenteropancreatic neuroendocrine tumors and lung carcinoids

Herrera-Martinez Aura D , Gahete Manuel D , Sanchez-Sanchez Rafael , Salas Rosa Ortega , Blanch Raquel Serrano , Salvatierra Juan , Luque Raul , Moreno Maria A Galvez , Castano Justo P

Neuroendocrine tumors (NETs) are uncommon neoplasms with increasing incidence and limited therapeutic options, wherein identification of new diagnostic/prognostic/therapeutic biomarkers is urgently required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of several cancers. Thus, we evaluated expression levels of SST/CORT/ghrelin system components in gastroenteropancreatic-neuroendocrine tumors (GEP-NETs...

ea0037oc7.5 | Neuroendocrinology and pituitary-basic | ECE2015

Not so giants: mice lacking both somatostatin and cortistatin have high GH levels, but show no changes in growth rate or IGF-I levels

Luque Raul M , Gahete Manuel D , Pedraza-Arevalo Sergio , Pozo-Salas Ana I , L-Lopez Fernando , de Lecea Luis , Cordoba-Chacon Jose , Castano Justo P

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...

ea0035p516 | Endocrine tumours and neoplasia | ECE2014

The truncated somatostatin receptor sst5TMD4 stimulates the production of pro-angiogenic factors in in vitro and in vivo breast cancer models

Luque Raul M , Duran-Prado Mario , Rincon-Fernandez David , Hergueta-Redondo Marta , Culler Michael D , Moreno-Bueno Gema , Gahete Manuel D , Castano Justo P

The presence of the truncated somatostatin receptor sst5TMD4 has been correlated with poor prognosis in breast cancer tumorsand its overexpression in breast cancer derived cell lines is associated with increased cell malignancy. The objective of this study was to examine the cellular and molecular mechanisms underlying this association in order to identify new molecular targets for diagnosis, prognosis or therapy of these tumors. Accordingly, in this study, a breast cancer der...