Fanconi Anemia complementation group C protein in metabolic disorders

Aging (Albany NY). 2018 Jun 21;10(6):1506-1522. doi: 10.18632/aging.101487.


Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA. We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging (glycine, citrulline, ornithine, L-asparagine, L-tyrosine, L-arginine, L-glutamine, L-leucine, L-isoleucine, L-valine, L-proline and L-alanine), Diabetes Mellitus (DM) (carbon monoxide, collagens, fatty acids, D-glucose, fumaric acid, 2-oxoglutaric acid, C3), inflammation (inosine, L-arginine, L-isoleucine, L-leucine, L-lysine, L-phenylalanine, hypoxanthine, L-methionine), and cancer ( L-methionine, sphingomyelin, acetyl-L-carnitine, L-aspartic acid, L-glutamic acid, niacinamide, phospho-rylethanolamine). We also found that FANCC can act in an FA-pathway-independent manner in tumor suppression. Collectively, featured-metabolic alterations are readouts of functional mechanisms underlying reduced tumorigenicity driven by FANCC, demonstrating close links among cancer, aging, inflammation and DM.

Keywords: Fanconi Anemia (FA); aging; cancer; diabetes; inflammation; metabolites.

MeSH terms

  • Animals
  • Biomarkers
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cloning, Molecular
  • Fanconi Anemia Complementation Group C Protein / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Metabolomics / methods*
  • Principal Component Analysis


  • Biomarkers
  • Fanconi Anemia Complementation Group C Protein