TY - JOUR T1 - Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201692 VL - 6 IS - 4 SP - e202201692 AU - Evelyn Andrades AU - Agustí Toll AU - Gustavo Deza AU - Sonia Segura AU - Ramón Gimeno AU - Guadalupe Espadas AU - Eduard Sabidó AU - Noemí Haro AU - Óscar J Pozo AU - Marta Bódalo AU - Paloma Torres AU - Ramon M Pujol AU - Inmaculada Hernández-Muñoz Y1 - 2023/04/01 UR - https://www.life-science-alliance.org/content/6/4/e202201692.abstract N2 - The initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads to lymph nodes. We report the reduced expression of small nucleolar RNAs in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (dyskerin, which stabilizes the small nucleolar RNAs) along the metastasis. DKC1 depletion in cSCC cells triggered lipid metabolism by altering the mevalonate pathway and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial-to-mesenchymal transition. Consistently, the expression of the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 1 was associated with pathological features of high metastatic risk in cSCC patients. Our data underpin the relevance of the mevalonate metabolism in metastatic dissemination and pave the possible incorporation of therapeutic approaches among the antineoplastic drugs used in routine patient care. ER -