Cytosolic 5'-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway.

Abstract

Cytosolic 5'-nucleotidase II (cN-II) is an allosteric catabolic enzyme that hydrolyzes IMP, GMP, and AMP. The enzyme can assume at least two different structures, being the more active conformation stabilized by ATP and the less active by inorganic phosphate. Therefore, the variation in ATP concentration can control both structure and activity of cN-II. In this paper, using a capillary electrophoresis technique, we demonstrated that a partial silencing of cN-II in a pulmonary carcinoma cell line (NCI-H292) is accompanied by a decrease in adenylate pool, without affecting the energy charge. We also found that cN-II silencing decreased proliferation and increased oxidative metabolism, as indicated by the decreased production of lactate. These effects, as demonstrated by Western blotting, appear to be mediated by both p53 and AMP-activated protein kinase, as most of them are prevented by pifithrin-α, a known p53 inhibitor. These results are in line with our previous observations of a shift towards a more oxidative and less proliferative phenotype of tumoral cells with a low expression of cN-II, thus supporting the search for specific inhibitors of this enzyme as a therapeutic tool for the treatment of tumors.

• Authors: Rossana Pesi, Simone Allegrini, Mercedes Garcia-Gil, Lucia Piazza, Roberta Moschini, Lars Petter Jordheim, Marcella Camici, Maria Grazia Tozzi
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 13 (Jun 29 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34209768 (Publication Type: Journal Article)

Chemical References

• Tumor Suppressor Protein p53
• AMP-Activated Protein Kinases
• 5'-Nucleotidase
• NT5C2 protein, human

Topics

• 5'-Nucleotidase (genetics, metabolism)
• AMP-Activated Protein Kinases (metabolism)
• Carcinoma, Mucoepidermoid (genetics, metabolism, pathology)
• Cell Line, Tumor
• Energy Metabolism (genetics)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Signal Transduction (genetics)
• Tumor Suppressor Protein p53 (metabolism)