Identification of metabolic changes leading to cancer
susceptibility in Fanconi anemia cells

J 2021

Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells

ABAD, Etna, Sara SAMINO, Robert L. GRODZICKI, Giovanni PAGANO, Marco TRIFUOGGI et. al.

Basic information

Original name

Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells

Authors

ABAD, Etna (724 Spain), Sara SAMINO (724 Spain), Robert L. GRODZICKI (840 United States of America), Giovanni PAGANO (380 Italy), Marco TRIFUOGGI (380 Italy), Dmitry GRAIFER (643 Russian Federation), David POTĚŠIL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Oscar YANES (724 Spain) and Alex LYAKHOVICH (643 Russian Federation)

Edition

Cancer Letters, Elsevier, 2021, 0304-3835

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

fulltext

Impact factor

Impact factor: 9.756

RIV identification code

RIV/00216224:14740/21:00119598

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.canlet.2020.12.010

UT WoS

000629990700018

Keywords in English

Fanconi anemia; Cancer predisposition; de novo purine biosynthesis; Fumarate; Purinosome; Metabolic reprogramming

Abstract

V originále

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.

Links

GBP206/12/G151, research and development project

Name: Centrum nových přístupů k bioanalýze a molekulární diagnostice

LM2015043, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90043, large research infrastructures

Name: CIISB

Citovat

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. 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.

@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.

Detailed Information on Publication Record