Resumen de Reguladores moleculares del control mitosis-diferenciación y su potencial uso como biomarcadores en carcinoma epidermoide de pulmón y cabeza y cuello
- español
El carcinoma epidermoide es el segundo tipo de cáncer más común y se desarrolla en epitelios estratificados, pero también en epitelios simples y pseudoestratificados como el pulmón. Los epitelios siguen un continuo proceso de autorrenovación donde es fundamental un equilibrio entre proliferación y diferenciación para mantener su estructura y funcionalidad. Existe un punto de control epidermoide que responde a alteraciones del ciclo celular y al daño genético, y que dispara la diferenciación terminal a través de un bloqueo en mitosis (Checkpoint Mitosis-Diferenciación, CMD). Los resultados de esta Tesis sugieren una función del CMD como barrera protectora contra la inestabilidad genómica y la capacidad metastática del carcinoma epidermoide. A su vez, este trabajo caracteriza el papel de la proteasa de SUMOilación SENP2 como un nuevo regulador del CMD. Finalmente, esta Tesis defiende la utilidad del modelo epitelial in vitro en medicina personalizada en cáncer y enfermedades raras, y aplicado a la búsqueda de nuevas estrategias terapéuticas.
Squamous cell carcinoma (SCC) is the second most frequent malignancy and it arises in stratified epithelium, but also in simple and pseudostratified epithelia as lung. Epithelia are continuously self-renewing and need to maintain a balance between proliferation and differentiation, keeping their structure and functionality. A mechanism known as Mitosis-Differentiation Checkpoint (MDC) responds to cell cycle disturbances and genetic damage, inducing terminal differentiation through mitotic slippage. The results of this Thesis suggest an MDC protective function as barrier against genomic instability and metastatic capacity of SCC. Furthermore, this work characterises the role of the SUMOylation protease SENP2 as a novel MDC regulator. Finally, this Thesis supports the application of the in vitro epithelial model in personalised medicine of cancer and rare diseases, and as a tool in the search of new pharmacological approaches.
- English
Squamous cell carcinoma (SCC) is the second most frequent malignancy and it arises in stratified epithelium, but also in simple and pseudostratified epithelia as lung. Epithelia are continuously self-renewing and need to maintain a balance between proliferation and differentiation, keeping their structure and functionality. A mechanism known as Mitosis-Differentiation Checkpoint (MDC) responds to cell cycle disturbances and genetic damage, inducing terminal differentiation through mitotic slippage. The results of this Thesis suggest an MDC protective function as barrier against genomic instability and metastatic capacity of SCC. Furthermore, this work characterises the role of the SUMOylation protease SENP2 as a novel MDC regulator. Finally, this Thesis supports the application of the in vitro epithelial model in personalised medicine of cancer and rare diseases, and as a tool in the search of new pharmacological approaches.
