Abstract
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.
Highlights
Aided by new biochemical and molecular biological tools, studies in cancer cell metabolism have expanded the understanding of the mechanisms and functional consequences of tumor-associated metabolic alterations at various stages of tumorigenesis
We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging, Diabetes Mellitus (DM), inflammation, and cancer ( L‐ methionine, sphingomyelin, acetyl‐L‐carnitine, L‐aspartic acid, L‐glutamic acid, niacinamide, phospho‐ rylethanolamine)
We found metabolites driven by FANCC are associated with cancer or aging and clearly with inflammation and diabetes, which are certainly part of mechanisms for reduced tumorigenicity initiated by FANCC
Summary
Aided by new biochemical and molecular biological tools, studies in cancer cell metabolism have expanded the understanding of the mechanisms and functional consequences of tumor-associated metabolic alterations at various stages of tumorigenesis. These alterations can affect the metabolite influx through conferring an increased ability to acquire the necessary nutrients. They can shape the manner the nutrients are preferentially assigned to metabolic pathways, which contribute to and lead to long-ranging effects on cellular fates [1]. Obesity is associated with an array of additional health problems, including an increased risk of insulin resistance, type 2 diabetes, fatty liver disease, atherosclerosis, degenerative disorders including dementia, airway diseases and cancers [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
