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@article{1824718, author = {Abad, Etna and Samino, Sara and Grodzicki, Robert L. and Pagano, Giovanni and Trifuoggi, Marco and Graifer, Dmitry and Potěšil, David and Zdráhal, Zbyněk and Yanes, Oscar and Lyakhovich, Alex}, article_number = {APR}, doi = {http://dx.doi.org/10.1016/j.canlet.2020.12.010}, keywords = {Fanconi anemia; Cancer predisposition; de novo purine biosynthesis; Fumarate; Purinosome; Metabolic reprogramming}, language = {eng}, issn = {0304-3835}, journal = {Cancer Letters}, title = {Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells}, url = {https://www.sciencedirect.com/science/article/pii/S0304383520306625?via%3Dihub}, volume = {503}, year = {2021} }
TY - JOUR ID - 1824718 AU - Abad, Etna - Samino, Sara - Grodzicki, Robert L. - Pagano, Giovanni - Trifuoggi, Marco - Graifer, Dmitry - Potěšil, David - Zdráhal, Zbyněk - Yanes, Oscar - Lyakhovich, Alex PY - 2021 TI - Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells JF - Cancer Letters VL - 503 IS - APR SP - 185-196 EP - 185-196 PB - Elsevier SN - 03043835 KW - Fanconi anemia KW - Cancer predisposition KW - de novo purine biosynthesis KW - Fumarate KW - Purinosome KW - Metabolic reprogramming UR - https://www.sciencedirect.com/science/article/pii/S0304383520306625?via%3Dihub N2 - Fanconi anemia (FA) is a chromosomal instability disorder of bone marrow associated with aplastic anemia, congenital abnormalities and a high risk of malignancies. The identification of more than two dozen FA genes has revealed a plethora of interacting proteins that are mainly involved in repair of DNA interstrand crosslinks (ICLs). Other important findings associated with FA are inflammation, oxidative stress response, mitochondrial dysfunction and mitophagy. In this work, we performed quantitative proteomic and metabolomic analyses on defective FA cells and identified a number of metabolic abnormalities associated with cancer. In particular, an increased de novo purine biosynthesis, a high concentration of fumarate, and an accumulation of purinosomal clusters were found. This was in parallel with decreased OXPHOS and altered glycolysis. On the whole, our results indicate an association between the need for nitrogenous bases upon impaired DDR in FA cells with a subsequent increase in purine metabolism and a potential role in oncogenesis. ER -
ABAD, Etna, Sara SAMINO, Robert L. GRODZICKI, Giovanni PAGANO, Marco TRIFUOGGI, Dmitry GRAIFER, David POTĚŠIL, Zbyněk ZDRÁHAL, Oscar YANES and Alex LYAKHOVICH. Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells. \textit{Cancer Letters}. Elsevier, 2021, vol.~503, APR, p.~185-196. ISSN~0304-3835. Available from: https://dx.doi.org/10.1016/j.canlet.2020.12.010.
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