Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma

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...

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Published in:Cancers 2022-07, Vol.14 (14), p.3432
Main Authors: Carmona-Carmona, Cristian Andres, Dalla Pozza, Elisa, Ambrosini, Giulia, Cisterna, Barbara, Palmieri, Marta, Decimo, Ilaria, Cuezva, José M, Bottani, Emanuela, Dando, Ilaria
Format: Article
Language:English
Subjects:
Adenocarcinoma
Apoptosis
Cancer
Cancer cells
Cell culture
Cell differentiation
Chemoresistance
Chemotherapy
Development and progression
Enzymes
Gene expression
Genetic aspects
Growth factors
Homeostasis
Metabolism
Metastases
Mitochondria
Mitochondrial DNA
Pancreatic cancer
Physiological aspects
Stem cells
Therapeutic targets
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14143432