PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma
Articolo
Data di Pubblicazione:
2023
Citazione:
PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma / F. Fontana, C. Macchi, M. Anselmi, A.S. Rizzuto, M. Ruscica, P. Limonta. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - (2023). [Epub ahead of print] [10.1016/j.bbadis.2023.166897]
Abstract:
Little is known about the metabolic regulation of cancer stem cells (CSCs) in melanoma. Here, we used A375 and WM115 cell lines to dissect the role of mitochondria in conferring CSC traits. Notably, we observed that A375 and WM115 melanospheres, known to be enriched in ABCG2+ CSCs, showed higher mitochondrial mass compared with their adherent counterpart. In particular, they displayed increased PGC1-α expression and oxidative phosphorylation (OXPHOS) complex levels, leading to a metabolic switch characterized by enhanced mitochondrial membrane potential, oxygen consumption, ATP synthesis and ROS production. Interestingly, PGC1-α silencing resulted in the suppression of CSC features, including clonogenic ability, migration, spheroid formation and ABCG2 enrichment. Similarly, XCT790 and SR-18292, two PGC1-α inhibitors, were able not only to reduce melanoma tumorigenicity and invasion but also to block melanosphere growth and propagation and ABCG2+ cell proliferation. In conclusion, improved mitochondrial biogenesis is associated with a stem-like phenotype in melanoma, and therapeutically targeting the mitochondria-enriched CSC subpopulation might overcome tumor progression.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Melanoma; Mitochondrial biogenesis; Oxidative phosphorylation (OXPHOS); PGC1-α; cancer stem cells (CSCs)
Elenco autori:
F. Fontana, C. Macchi, M. Anselmi, A.S. Rizzuto, M. Ruscica, P. Limonta
Link alla scheda completa: