Purine-Metabolising Enzymes and Apoptosis in Cancer

被引:51
作者
Camici, Marcella [1 ]
Garcia-Gil, Mercedes [2 ]
Pesi, Rossana [1 ]
Allegrini, Simone [1 ]
Tozzi, Maria Grazia [1 ]
机构
[1] Dipartimento Biol, Unita Biochim, Via S Zeno 51, I-56127 Pisa, Italy
[2] Dipartimento Biol, Unita Fisiol Gen, Via S Zeno 31, I-56127 Pisa, Italy
关键词
purine salvage; apoptosis; CD73; cN-II; ADA; PNP; HPRT; IMPDH; SAMHD1; MTH1; ADENOSINE-DEAMINASE ACTIVITY; INOSINE 5'-MONOPHOSPHATE DEHYDROGENASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; AICARDI-GOUTIERES SYNDROME; CELL-CYCLE ARREST; GUANINE-NUCLEOTIDE DEPLETION; RECEPTOR MEDIATES APOPTOSIS; RESTRICTION FACTOR SAMHD1; 5'-NUCLEOTIDASE CN-II; DNA MISMATCH REPAIR;
D O I
10.3390/cancers11091354
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. In this review, we describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme. The enzymes discussed are: ectosolic and cytosolic 5'-nucleotidases, purine nucleoside phosphorylase, adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase, and inosine-5'-monophosphate dehydrogenase, as well as recently described enzymes particularly expressed in tumour cells, such as deoxynucleoside triphosphate triphosphohydrolase and 7,8-dihydro-8-oxoguanine triphosphatase.
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页数:27
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