Abstract
Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP7 has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP6K) isoforms regulate IP7 synthesis in mammals. Genomic deletion or enzymic inhibition of IP6K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP6K1 could therefore be a useful target in anticancer treatment. Here, we summarize the current understanding that established IP6K1 and the other IP6K isoforms as possible targets for cancer therapy. However, it will be necessary to determine whether pharmacological inhibition of IP6K is safe enough to begin clinical study. The development of safe and selective inhibitors of IP6K isoforms is required to minimize undesirable effects.
Highlights
Inositol is a ubiquitous polyol involved in a number of essential processes in living organisms.Myo-inositol is physiologically the most important of nine isomers and is the precursor of a bewildering number of complex inositol-containing molecules, including inositol phosphates [1,2].Inositol compounds are essential for many biological functions in living cells: membrane biogenesis [3], trafficking [4], signal transduction, and regulation of gene expression [5]
It is metabolized to a large number of additional inositol polyphosphates that function as cell signals [9]
Inositol hexakisphosphate is the building block to which successive phosphate groups are added to yield inositol pyrophosphates (PP-IPs) [15,16], where as many as one or two energetic di(β)phosphates bonds are crammed around the six-carbon inositol ring [17]
Summary
Inositol is a ubiquitous polyol involved in a number of essential processes in living organisms. Inositol hexakisphosphate (IP6 ), known as phytic acid, is the most abundant inositol polyphosphate found in eukaryotes, identified as the principal phosphate-storage molecule in plant seeds [10,11]. It is involved in regulation of trafficking [12] as well as in several nuclear events [13,14]. Inositol hexakisphosphate is the building block to which successive phosphate groups are added to yield inositol pyrophosphates (PP-IPs) [15,16], where as many as one or two energetic di(β)phosphates bonds are crammed around the six-carbon inositol ring [17] This class of molecule recently gained appreciation as critical modulators of a huge. PP-IPs show high turnover as their intracellular levels fluctuate significantly in various pathological disorders, including cancer [20]
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