Abstract
Background: Thyroid cancer is the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most common (85–90%) among all the different types of thyroid carcinomas. Cancer cells show metabolic alterations and, due to their rapid proliferation, an accumulation of reactive oxygen species, playing a fundamental role in cancer development and progression. Currently, the crosstalk among thyrocytes metabolism, redox balance and oncogenic mutations remain poorly characterized. The aim of this study was to investigate the interplay among metabolic alterations, redox homeostasis and oncogenic mutations in PTC-derived cells. Methods: Metabolic and redox profile, glutamate-cysteine ligase, glutaminase-1 and metabolic transporters were evaluated in PTC-derived cell lines with distinguished genetic background (TPC-1, K1 and B-CPAP), as well as in an immortalized thyroid cell line (Nthy-ori3-1) selected as control. Results: PTC-derived cells, particularly B-CPAP cells, harboring BRAF, TP53 and human telomerase reverse transcriptase (hTERT) mutation, displayed an increase of metabolites and transporters involved in energetic pathways. Furthermore, all PTC-derived cells showed altered redox homeostasis, as reported by the decreased antioxidant ratios, as well as the increased levels of intracellular oxidant species. Conclusion: Our findings confirmed the pivotal role of the metabolism and redox state regulation in the PTC biology. Particularly, the most perturbed metabolic phenotypes were found in B-CPAP cells, which are characterized by the most aggressive genetic background.
Highlights
Metabolic reprogramming in tumor has been reported as one of the “hallmarks of cancer”, providing proliferating cancer cells with the bioenergetic and biosynthetic metabolites and biosynthetic advantages needed for neoplastic transformation [1]
The results revealed an increase of metabolites associated with glycolysis [Glucose-6-phosphate/fructose-6-phosphate (G6P/F6P), dihydroxyacetone phosphate (DHAP), glyceraldheide-3-phosphate (GAP), 2/3-phosphoglycerate
(2/3PG), and phosphoenolpyruvate (PEP)] and a decrease of fructose-1,6-phosphate (F1, 6P) and lactate in B-CPAP compared to both control and other papillary thyroid carcinoma (PTC)-derived cells (Figure 1)
Summary
Metabolic reprogramming in tumor has been reported as one of the “hallmarks of cancer”, providing proliferating cancer cells with the bioenergetic and biosynthetic metabolites and biosynthetic advantages needed for neoplastic transformation [1]. This adaptation results in dysregulation of several pathways, including glycolysis, glutaminolysis, citric acid cycle, pentose phosphate shunt, and lipid metabolism [2]. All PTC-derived cells showed altered redox homeostasis, as reported by the decreased antioxidant ratios, as well as the increased levels of intracellular oxidant species.
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