Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
EntityUAM. Departamento de Biología Molecular
10.3390/cancers14143432Cancers 14.14 (2022): 3432
SubjectsDynamin; Messenger RNA; Mitochondrial DNA; Small interfering RNA; Biología y Biomedicina / Biología
Rights© 2022 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem cells (CSCs). CSCs present a heterogeneous metabolic profile that might be supported by an adaptation of mitochondrial function; however, the role of this organelle in the development and maintenance of CSCs remains controversial. To determine the role of mitochondria in CSCs over longer periods, which may reflect more accurately their quiescent state, we studied the mitochondrial physiology in CSCs at short-, medium-, and long-term culture periods. We found that CSCs show a significant increase in mitochondrial mass, more mitochondrial fusion, and higher mRNA expression of genes involved in mitochondrial biogenesis than parental cells. These changes are accompanied by a regulation of the activities of OXPHOS complexes II and IV. Furthermore, the protein OPA1, which is involved in mitochondrial dynamics, is overexpressed in CSCs and modulates the tumorsphere formation. Our findings indicate that CSCs undergo mitochondrial remodeling during the stemness acquisition process, which could be exploited as a promising therapeutic target against pancreatic CSCs
Google Scholar:Carmona-Carmona, Cristian Andres - Dalla Pozza, Elisa - Ambrosini, Giulia - Cisterna, Barbara - Palmieri, Marta - Decimo, Ilaria - Cuezva Marcos, José Manuel - Bottani, Emanuela - Dando, Ilaria
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