The Hormones and Cancer research group is a consolidated group of the IMIBIC comprised by basic, translational, and clinical researchers. We investigate the cellular and molecular principles underlying the natural processes of neuroendocrine-metabolic regulation and their dysfunctions in tumors and cancer. The group pays special attention to the role played by certain neuropeptide/receptor systems and their regulation by distinct mechanisms, especially alternative splicing and its related RNA controlling processes and associated signalling pathways, at the onco-endocrine interface. The original focus of our group laid on the study of pituitary cell biology, particularly growth hormone (GH)-producing somatotropes and their regulatory signals (somatostatin, cortistatin, GHRH, ghrelin, Kisspeptins, etc.) and receptors (SST1-5, GHRHR, GHSR1, KISS1R), and signalling pathways. This line evolved to study pituitary neuroendocrine tumors (PitNETs) and expanded definitely with the discovery of novel, abnormal splicing variants (SST5TMD4, In1-ghrelin) and the study of their pathophysiological role in somatotropes and other endocrine cell types (eg. corticotropes, gonadotropes, pancreatic beta cells) and, broadly, in tumor development and metabolic dysfunction. Currently, our work is centred in the pathophysiology of neuroendocrine tumors (NETs) from pancreatic, gastrointestinal and lung origin, and of pancreatic ductal adenocarcinoma (PDAC), wherein we investigate the actions of diverse molecular regulatory systems (including somatostatin, ghrelin, etc.) and the specific role of alternative splicing and RNA biology.
To achieve our goals, we use a wide range of techniques, including primary cultures of normal and tumor cells, cell lines, genetically modified animals, measurements of peptides, hormones, second messengers and gene expression of diverse molecular components, particularly of the spliceosome machinery, as well as dynamic imaging of molecular trafficking, confocal microscopy in living cells, etc. We are developing and applying biocomputational approaches to explore the spliceosomic landscape in different experimental and clinical settings with the aim of further understanding the contribution of splicing and RNA metabolism to cancer and other diseases.
Our studies have led to the discovery and characterization of new receptors, splicing variants, functions and mechanisms of action for different neuroendocrine-metabolic signals and drugs controlling hormone secretion, tumorigenesis or cell death and survival in normal and pathological conditions, such as metabolic dysregulations (diabetes, obesity) and cancer (PitNETs, NETs, pancreatic cancer, and breast, prostate, and liver cancers, among others). Our ultimate aim is to contribute to the discovery of novel biomarkers for early detection, improved diagnosis and predictive prognosis of the tumors studied, as well as to identify actionable targets for the design of innovative personalized therapeutic strategies, which would jointly enable the advancement of precision medicine in NETs and pancreatic cancer.
CIBERobn Physiopathology of Obesity and Nutrition
GETNE - Spanish Group of Neuroendocrine Tumours – Spanish Society of Medical Oncology
TransBioNet – Spanish Bioinformatics Network for Clinical Research
Area of Knowledge of Neuroendocrinology – Spanish Society of Endocrinology and Nutrition
Neuroendocrinology Work Group – Andalusian Society of Endocrinology, Diabetes and Nutrition
REMAH - Spanish Molecular Registry of Hypophyseal Adenomas
PAIDI BIO-139 Cellular and molecular endocrinology (Andalusian Plan for Research, Development and Innovation - PAIDI)
ceiA3 - Agrifood Campus of International Excellence
- Cellular and molecular endocrine oncology
- pancreatic cancer
- neuroendocrine tumors
- pituitary tumors
- alternative splicing
5 most relevant publicactions (2017-2019)
1- Vázquez-Borrego MC, Fuentes-Fayos AC, Venegas-Moreno E, Rivero-Cortés E, Dios E, Moreno-Moreno P, Madrazo-Atutxa A, Remón P, Solivera J, Wildemberg LE, Kasuki L, López-Fernandez JM, Gadelha MR, Gálvez-Moreno MA, Soto-Moreno A, Gahete MD, Castaño JP*, Luque R; Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features. CANCERS.11.10.1439. DOI: 10.3390/cancers11101439. IF: 6,162. (D2 Q1; Oncology) *Co-senior author
2- Günther T, Tulipano G, Dournaud P, Bousquet C, Csaba Z, Kreienkamp HJ, Lupp A, Korbonits M, Castaño JP, Wester HJ, Culler MD, Melmed S, Schulz S. International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature. Pharmacol Rev 2018, 70(4):763-835. IF: 18.886. (D1; Pharmacology & pharmacy)
3- Hormaechea-Agulla D, Gahete MD, Jiménez-Vacas JM, Gómez-Gómez E, Ibáñez-Costa A, L-López F, Rivero-Cortés E, Sarmento-Cabral A, Valero-Rosa J, Carrasco-Valiente J, Sánchez-Sánchez R, Ortega-Salas R, Moreno MM, Tsomaia N, Swanson SM, Culler MD, Requena MJ, Castaño JP*, Luque RM. The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness. Mol Cancer 2017, 16(1):146. IF: 10.679 (D1; Oncology) *Co-senior author
4- Herrera-Martínez AD, Gahete MD, Sánchez-Sánchez R, Salas RO, Serrano-Blanch R, Salvatierra Á, Hofland LJ, Luque RM, Gálvez-Moreno MA, Castaño JP. The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features. Lung Cancer 2017, 109:128-136. FI: 4.599. (Q1; Respiratory System)
5- Gahete MD, Del Rio-Moreno M, Camargo A, Alcalá-Diaz JF, Alors-Pérez E, Delgado-Lista J, Reyes O, Ventura S, Perez-Martínez P, Castaño JP*, Lopez-Miranda J, Luque RM. Changes in splicing machinery components influence, precede, and early predict the development of type 2 diabetes: From the CORDIOPREV study. EBioMedicine 2018, 3964(18)30479-1. IF: 6.183. (D1; Medicine, Research & Experimental area) *Co-senior author
1. Alterations in the alternative splicing machinery in pancreatic cancer: Identifications of novel diagnostic, prognostic and therapeutic biomarkers. BFU2016-80360-R. PI: Justo P Castaño. Ministerio de Economía y Competitividad (MINECO). 2017-2019. 181.500€
2. Spliceosomic strategy to improve the diagnostic, classification and treatment of pancreatic neuroendocrine tumors. G1909. PI: Justo P Castaño. Beca GETNE 2019. 2020-2022. 60.000 €
3. IMIBIC Fellowship Programme for Personalised and Precision Medicine (P2Med): H2020 MSCA COFUND FP 2018. GA nr: 847468. Coordinator: Justo P Castaño. (IMIBIC). 2019-2024. EC Funding: 662.040 €. (Total cost 1.183.680 €).
4. Promoting STEM vocations from Biomedicine. FCT-18-13958. PI: Justo P Castaño. FECYT. 2019-2020. 20.000€.
5. Spliceosomic strategy in NETs for the improvement of diagnostic, classification and treatment. FERP2019. PI: Justo P Castaño. Fundación Eugenio Rodríguez Pascual 2019. 2019-2020. 7.000 €
6. Analysis of the in vitro combination of trastuzumab and lirilumab in breast cancer. Involvement of alternative splicing processes. PI: Cristina Morales Estévez. Sociedad Española de Oncología Médica (Beca FSEOM/BMS - Proyectos de investigación traslacional en Inmuno-Oncología 2018). 2019-2020. 40.000€.
7. Diagnosis and personalized postoperative prognosis of human gliomas using a new interactive approach. PI-0143-2016. PI: Juan Solivera Vela. Consejería de Salud (Junta de Andalucía). 2017-2019. 46.970,42 €
8. Molecular and functional characterization of bladder cancer: search of novel therapies. PI: Raúl M Luque. Eli Lilly & Company. 46.200 €. 2019-20.
9. Ghrelin-O-acyl-Transferase (GOAT): New Biomarker for the screening of prostate cancer. DTS18/00131. PI: Raúl M Luque. Instituto de Salud Carlos III. Proyectos de Desarrollo Tecnológico en Salud. 2018-2020. 88.550€.
10. Ghrelin-O-aciltransferase (GOAT): new biomarker for prostate cancer. (FIPSE Project 3188-17). PI: Raúl M Luque. 2018-2019. 30.000€.
1. Isoforms of the human somatostatin receptor type 5 produced by alternative processing and pairs of oligonucleotides for detection by PCR. Castaño JP, Durán Prado M, Martínez Fuentes AJ, Vázquez-Martínez R, García Navarro S, Gracia-Navarro F, Malagón MM. P200502701.
2. Ghrelin variant and its use. Luque RM, Castaño JP, Gahete MD, Gracia-Navarro F, Martínez-Fuentes AJ, Córdoba-Chacón J, Benito P, Kineman RD. P201030905.
3. Ghrelin-O-acyltransferase (GOAT) and its use. Castaño JP, Luque RM, Gahete MD, Hormaechea-Agulla D, Requena-Tapia MJ, Gómez-Gómez E, Carrasco-Valiente J, Ibáñez-Costa A, Moreno MM, Valero-Rosa J. P201531731 - PCT/ES2016/070844
4. Non-invasive diagnostic method for cancer. Castaño JP, Luque RM, Gahete MD, Ibáñez-Costa A, Hormaechea-Agulla D, Jiménez-Vacas JM, Sarmento-Cabral A, L-López F, Requena-Tapia MJ, Gómez-Gómez E, Carrasco-Valiente J.P201631606 - PCT/ES2017/070797
5. Peptides derived from the truncated somatostatin receptor sst5TMD4 as biomarkers and therapeutic targets in tumor pathologies. Luque RM, Castaño JP, Gahete MD, del Río-Moreno M, Alors-Pérez E. P201730702 - PCT/ES2018/070361
6. Method for the prediction and prognostic of the development of type 2 diabetes mellitus. Castaño JP, Luque RM, Gahete MD, López-Miranda J, Pérez-Martínez P, Delgado-Lista J, García-Ríos A, Alcalá-Díaz JF, Yubero-Serrano E, Camargo-García A, del Río-Moreno M, Alors-Pérez E, Ventura-Soto S, Reyes-Pupo O. P201831095
7. Method for the diagnosis, prognosis and treatment of neuroendocrine tumors. Castaño JP, Luque RM, Gahete MD, Pedraza-Arévalo S, del Río-Moreno M, Alors-Pérez E, Gálvez-Moreno MA, Herrera-Martínez A, Serrano-Blanch R. P201831039
8. Method for the diagnosis and prognosis of the development of prostate cancer. Castaño JP, Luque RM, Gahete MD, Jiménez-Vacas JM, Sarmento-Cabral A, L-López F, Requena-Tapia MJ, Gómez-Gómez E, Carrasco-Valiente J. P201930104
9. Method of obtaining useful data for the diagnosis, stratification and / or follow-up of patients with rheumatoid arthritis. Castaño JP, Luque RM, López-Pedrera R, Pérez-Sánchez C, Collantes-Estévez E, Ortega-Castro R, Ibáñez-Costa A, Pedraza-Arévalo S, del Río-Moreno M, Barbarroja-Puerto N, Jimenez-Gomez Y. P201930123
10. Method for the diagnosis and prognosis of the development of brain tumors. Luque RM, Gahete MD, Fuentes-Fayos AC, Castaño JP, Ibáñez-Costa A, Vázquez-Borrego MC, López-López F, Blanco-Acebedo C, Solivera-Vela J, Toledano-Delgado A, Gálvez-Moreno MA. P201931147.