Polyamines and related signaling pathways in cancer
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Cancer Cell International Open Access
REVIEW
Polyamines and related signaling pathways in cancer Jiajing Li1,2, Yan Meng2, Xiaolin Wu2 and Yuxin Sun1*
Abstract Polyamines are aliphatic compounds with more than two amino groups that play various important roles in human cells. In cancer, polyamine metabolism dysfunction often occurs, and regulatory mechanisms of polyamine. This review summarizes the existing research on the metabolism and transport of polyamines to study the association of oncogenes and related signaling pathways with polyamines in tumor cells. Drugs that regulate enzymes have been developed for cancer treatment, and in the future, more attention should be paid to treatment strategies that simultaneously modulate polyamine metabolism and carcinogenic signaling pathways. In addition, the polyamine pathway is a potential target for cancer chemoprevention. As an irreversible suicide inhibitor of the ornithine decarboxylase (a vital enzyme of polyamine synthesis), Difluoro-methylornithine had been shown to have the chemoprevention effect on cancer. Therefore, we summarized and analyzed the chemoprophylaxis effect of the difluoromethylornithine in this systematic review. Keywords: Polyamine, Cancer, Metabolism, Signaling pathway, Oncogene, ODC, SSAT, DFMO Background Polyamines are polycationic alkylamines commonly found in all living cells, of which the most common are putrescine, spermine, and spermine (in millimolar concentrations) [1, 2]. The flexibility in their charge distribution allows polyamines to combine with various negatively charged macromolecules, including DNA, RNA, proteins, and acidic phospholipids [3, 4]. Therefore, they play an important role in cell growth, proliferation, differentiation, migration, gene regulation, and the synthesis of proteins and nucleic acids, in addition to maintaining chromatin structure, regulating ion channels, maintaining membrane stability, and scavenging free radicals [5–7]. It has been shown that increased intracellular polyamine concentrations are associated with cell proliferation and tumorigenesis [8–14]. Polyamine metabolism is often dysregulated in cancers. In addition, *Correspondence: [email protected] 1 Department of Otorhinolaryngology‐Head and Neck Surgery, China‐ Japan Union Hospital, Jilin University, Changchun, Jilin Province, China Full list of author information is available at the end of the article
the polyamine pathway is a downstream target for many oncogenes [15–17]. In normal physiological conditions, polyamines are regulated by a complex network of biosynthesis, catabolism, and transport systems (Fig. 1).
Polyamine synthesis and metabolism Polyamine biosynthesis
Excess nitrogen and ammonia produced by protein breakdown or nitrogen compound synthesis in vivo can be eliminated by the urea cycle. During this process, arginine is catalyzed by arginase to produce ornithine, the substrate for the synthesis of urea and polyamines. The main pathway of polyamine biosynthesis is the decarboxylation of ornithine catalyzed by ornithine de
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