ECE2022 Poster Presentations Endocrine-Related Cancer (41 abstracts)
Somatostatin receptor splicing variant SST5TMD4 overexpression in glioblastoma is associated to poor survival, increased aggressiveness features and somatostatin analogs resistance
Jesus Perez Gomez 1,2,3,4 , Antonio C. Fuentes-Fayos 1,2,3,4 , Miguel E. G-Garcia 1,2,3,4 , Annabel Peel 5 , Cristóbal Blanco Acevedo 1,2,6 , Juan Solivera Vela 1,2,6 , Alejandro Ibáñez Costa 1,2,3,4 , Manuel David Gahete Ortiz 1,2,3,4 , Justo P. Castaño 1,2,3,4 & Raúl M. Luque 1,2,3,4
1Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain; 2University of Cordoba, Department of Cell Biology, Physiology, and Immunology, University of Cordoba, Córdoba, Spain; 3Reina Sofia University Hospital (HURS), Córdoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Córdoba, Spain; 5Cardiff University, School of Biosciences, Cardiff, United Kingdom; 6Reina Sofia University Hospital, Department of Neurosurgery, Córdoba, Spain
Glioblastoma (GBM; grade IV astrocytoma) is the one of the most malignant and lethal endocrine-related cancers worldwide. Current standard treatment consists of surgery followed by radiotherapy and/or chemotherapy; however, this is only a palliative approach with a mean post-operative survival of scarcely ~12-15 months. Therefore, the identification of novel therapeutic targets to treat this devastating pathology is urgently needed. In this context, the truncated splicing-variant of the somatostatin receptor subtype 5 (SST5TMD4), which is produced by aberrant alternative splicing, has been demonstrated to be overexpressed and associated with increased aggressiveness features in several endocrine-related cancers/tumors. However, the presence, functional role, and associated molecular mechanisms of SST5TMD4 in GBM have not been yet explored. Therefore, we performed herein a comprehensive analysis to characterize the expression and pathophysiological role of SST5TMD4 in human GBM. We demonstrated that SST5TMD4 was significantly overexpressed (at mRNA and protein levels) in human GBM tissues (n=47) compared to non-tumor brain tissues (control; n=15) and grade III-astrocytoma patients (n=9). Remarkably, SST5TMD4 expression was significantly associated with poor overall survival and recurrent tumors in GBM patients. Moreover, in vitro SST5TMD4 overexpression (by specific plasmid) increased, whereas SST5TMD4 silencing (by specific siRNA) decreased, key malignant features (i.e., proliferation and migration capacity) of GBM cells (U-87 MG/U-118 MG models). Furthermore, SST5TMD4 overexpression in GBM cells altered the activity of multiple key signaling-pathways associated with tumor aggressiveness and progression (AKT, JAK-STAT, NF-κB and TGFβ routes), and its silencing sensitized GBM cells to the antitumor effect of pasireotide (a somatostatin analog). Altogether, these results demonstrated that SST5TMD4 is overexpressed and associated with enhanced malignancy features in human GBMs and revealed its potential utility as a novel and useful diagnostic and prognostic biomarker and as a potential target in the future development of therapeutic approaches in patients with this devastating endocrine-related cancer, offering a clinically relevant opportunity that should be tested for use in humans.
Fundings: Spanish Ministry of Science, Innovation and Universities (PID2019-105564RB-I00, FPU16-05059, FPU20-03954, FPU18-06009), Junta de Andalucía (P20_00442, PEER-0048-2020, BIO-0139) and CIBERobn.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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