RT Journal Article
SR Electronic
T1 Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201692
DO 10.26508/lsa.202201692
VO 6
IS 4
A1 Evelyn Andrades
A1 Agustí Toll
A1 Gustavo Deza
A1 Sonia Segura
A1 Ramón Gimeno
A1 Guadalupe Espadas
A1 Eduard Sabidó
A1 Noemí Haro
A1 Óscar J Pozo
A1 Marta Bódalo
A1 Paloma Torres
A1 Ramon M Pujol
A1 Inmaculada Hernández-Muñoz
YR 2023
UL https://www.life-science-alliance.org/content/6/4/e202201692.abstract
AB 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.