The telomerase/shelterin system is impaired in acromegaly and Cushing´s disease: Potential pathophysiological relevance
Year: 2026
Type: article
Abstract: Pituitary Tumours (PiTs) present significant challenges in diagnosis and treatments due to their heterogeneity, complex pathophysiology and endocrine comorbidities. Current therapies (i.e., surgery/radiotherapy/pharmacological treatment) frequently become ineffective over time, leading to low quality of life and high recurrence rates. Therefore, identifying alternative medical tools for these rare pathologies is crucial. The alteration of the telomerase/shelterin (TEL/SHEL) molecular complexes has been associated with cancer pathophysiology and progression; however, their role in PiTs remains poorly understood. Herein, we uncovered a profound dysregulation in the expression of key components of the TEL/SHEL systems in growth-hormone, adrenocorticotropic-hormone, and prolactin-hormone producing PiTs [GHomas (n = 50)/ACTHomas (n = 19)/PRLomas (n = 6), respectively] versus non-tumour pituitary tissues (n = 10), and identified critical dysregulated components in GHomas, ACTH, and PRLomas, some of them associated with key clinical features in GHomas (i.e., sinus-invasion/visual-alteration/cephalea, etc.). Presurgery treatment is likely not a confounding variable in the alterations observed in the TEL/SHEL system in PiTs. Moreover, we demonstrated that TEL activity inhibition (using BIBR1532) in primary-patient cell-cultures and cell-line models (GH3/AtT-20) might serve as a potential therapeutic tool by reducing cell-proliferation and stem-cell capacity through the modulation of key oncogenic processes, including GH/ACTH synthesis, cell-cycle, and DNA Damage Repair (DDR) pathways. Notably, we also demonstrated that BIBR1532, in combination with somatostatin-analogues, exerted a synergistic/additive anti-proliferative effect in GH3 and AtT-20 cells. Altogether, we demonstrate a profound TEL/SHEL-associated molecular dysregulation in GHomas and ACTHomas, which could serve as a potential source of novel diagnostic/prognostic biomarkers and therapeutic targets, offering a clinically relevant opportunity worth to be explored in humans.
Source: Biomedicine & Pharmacotherapy
Authors: Miguel E. G-García, Ana S. De la Rosa-Herencia, Ignacio Gil-Duque, Laura Arroyo-Millán, Eva Venegas, Aura D. Herrera-Martínez, María Ortega-Bellido, Miguel A. Núñez- Santos, Antonio J. Montero-Hidalgo, Inmaculada Gavilán, Judith López-Fernández, José G. Oliva-García, Alberto Moreno-Carazo, Irene Iglesias-Lozano, Marta Ordoñez-Carmona, Elena Dios, Pablo Remón, Miguel A. Japón, Juan Solivera, David A. Cano, Manuel D. Gahete, Álvaro Flores-Martínez, María Ángeles Gálvez-Moreno, Alfonso Soto-Moreno, Antonio C. Fuentes-Fayos, Raúl M. Luque
Institutions: Instituto Maimónides de Investigación Biomédica de Córdoba, University of Córdoba, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Hospital Universitario Reina Sofía, Hospital Universitario Puerta del Mar, Universidad de La Laguna, Hospital Universitario de Canarias, Hospital Universitario Nuestra Señora de Candelaria
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,610
Funders: Fundación SEEN, Ministerio de Ciencia, Innovación y Universidades, Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Fundación Pública Andaluza Progreso y Salud, Consejería de Salud y Consumo, Junta de Andalucía, Hospital Universitario Virgen del Rocío
OpenAlex ID: W7160868395