Naslov
Nicotinamide N-methyltransferase in acquisition of stem cell properties and therapy resistance in cancer
(Nicotinamide N-methyltransferase in acquisition of stem cell properties and therapy resistance in cancer)

Autori
Novak Kujundžić, Renata ; Prpić, Marin ; Ðaković, Nikola ; Dabelić, Nina ; Tomljanović, Marko ; Mojzeš, Anamarija ; Fröbe, Ana ; Gall Trošelj, Koraljka

Izvornik
International journal of molecular sciences (1422-0067) 22 (2021), 11; 5681, 21

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
nicotinamide N-methyltransferase ; nicotinamide adenine dinucleotide ; aldehyde oxidase ; cancer ; epigenetic reprogramming ; senescence ; stem cell properties ; therapy resistance

Sažetak
The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the mainte-nance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylationof nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further me- tabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMTis important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly– adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriatelyhigh expression and activity of NNMT, commonly present in various types of cancer, has the potentialto disrupt NAD+homeostasis and cellular methylation potential. Largely overlooked, in the contextof cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT’s positive effecton cellular NAD+flux by stalling liberation of NAM and reducing NAD+synthesis in the salvagepathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasionof a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties.All these phenomena are related to therapy resistance and worse clinical outcomes

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA