Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer

Author:

Allegrini Simone123ORCID,Camici Marcella1ORCID,Garcia-Gil Mercedes234ORCID,Pesi Rossana1ORCID,Tozzi Maria Grazia1ORCID

Affiliation:

1. Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy

2. Centro di Ricerca Interdipartimentale Nutrafood “Nutraceuticals and Food for Health”, Università di Pisa, 56126 Pisa, Italy

3. CISUP, Centro per l’Integrazione Della Strumentazione Dell’Università di Pisa, 56127 Pisa, Italy

4. Unità di Fisiologia Generale, Dipartimento di Biologia, Università di Pisa, Via San Zeno 31, 56127 Pisa, Italy

Abstract

Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are characterized by an increased “de novo” synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes of purine metabolism are the targets of drugs as antineoplastic agents, and a better knowledge of the mechanisms underlying their regulation would be of great help in finding new therapeutic approaches. The mammalian target of the rapamycin (mTOR) signaling pathway, which is often activated in cancer cells, promotes anabolic processes and is a major regulator of cell growth and division. Among the numerous effects exerted by mTOR, noteworthy is its empowerment of the “de novo” synthesis of nucleotides, accomplished by supporting the formation of purinosomes, and by increasing the availability of necessary precursors, such as one-carbon formyl group, bicarbonate and 5-phosphoribosyl-1-pyrophosphate. In this review, we highlight the connection between purine and mitochondrial metabolism, and the bidirectional relation between mTOR signaling and purine synthesis pathways.

Funder

University of Pisa

Publisher

MDPI AG

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