Cytidine deaminase-dependent mitochondrial biogenesis as a potential vulnerability in pancreatic cancer cells
Year: 2024
Type: article
Abstract: Cytidine deaminase (CDA) converts cytidine and deoxycytidine into uridine and deoxyuridine as part of the pyrimidine salvage pathway. Elevated levels of CDA are found in pancreatic tumors and associated with chemoresistance. Recent evidence suggests that CDA has additional functions in cancer cell biology. In this work, we uncover a novel role of CDA in pancreatic cancer cell metabolism. CDA silencing impairs mitochondrial metabolite production, respiration, and ATP production in pancreatic cancer cells, leading to a so-called Pasteur effect metabolic shift towards glycolysis. Conversely, we find that CDA expression promotes mitochondrial biogenesis and oxidative phosphorylation, independently of CDA deaminase activity. Furthermore, we observe that patient primary cells overexpressing CDA are more sensitive to mitochondria-targeting drugs. Collectively, this work shows that CDA plays a non-canonical role in pancreatic cancer biology by promoting mitochondrial function, which could be translated into novel therapeutic vulnerabilities.
Source: Communications Biology
Institutions: Centre National de la Recherche Scientifique, Inserm, Centre de Recherches en Cancérologie de Toulouse, Université de Toulouse, La Ligue Contre le Cancer, Université Toulouse III - Paul Sabatier, Institut National des Sciences Appliquées de Toulouse, Toulouse Biotechnology Institute, Bio & Chemical Engineering, MetaboHUB, RESTORE, Hôpital Rangueil, Aix-Marseille Université, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
OpenAlex ID: W4402049933