Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Abstract

Oncocytic thyroid cancer is characterized by the aberrant accumulation of abnormal mitochondria in the cytoplasm and a defect in oxidative phosphorylation. We performed metabolomics analysis to compare metabolic reprogramming among the oncocytic and non-oncocytic thyroid cancer cell lines XTC.UC1 and TPC1, respectively, and a normal thyroid cell line Nthy-ori 3-1. We found that although XTC.UC1 cells exhibit higher glucose uptake than TPC1 cells, the glycolytic intermediates are not only utilized to generate end-products of glycolysis, but also diverted to branching pathways such as lipid metabolism and the serine synthesis pathway. Glutamine is preferentially used to produce glutathione to reduce oxidative stress in XTC.UC1 cells, rather than to generate α-ketoglutarate for anaplerotic flux into the TCA cycle. Thus, growth, survival and redox homeostasis of XTC.UC1 cells rely more on both glucose and glutamine than do TPC1 cells. Furthermore, XTC.UC1 cells contained higher amounts of intracellular amino acids which is due to higher expression of the amino acid transporter ASCT2 and enhanced autophagy, thus providing the building blocks for macromolecules and energy production. These metabolic alterations are required for oncocytic cancer cells to compensate their defective mitochondrial function and to alleviate excess oxidative stress.

The Role of De novo Serine Biosynthesis from Glucose in Papillary Thyroid Cancer

“…Recent study compared oncocytic and non-oncocytic thyroid cancer, and revealed higher glucose uptake and rerouting of glutamine to glutathione for redox homeostasis in the oncocytic cell line to compensate for its defective mitochondrial function. 19) Moreover, 1 H-NMR spectroscopy has been used to show that oxidative stress alters the metabolic profile in thyroid cancer, with increases in lactate and aromatic amino acids and a decrease in citrate. 18) However, the de novo serine biosynthetic pathway from glucose is not fully understood in differentiated thyroid cancer.…”

Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer

“…These defects have been studied in oncocytic thyroid cancer, which is characterized by the accumulation of abnormal mitochondria in the cytoplasm. Recently, a study comparing oncocytic and non-oncocytic thyroid cancer, showed higher glucose uptake and rerouting of glutamine to glutathione for redox homeostasis in the oncocytic cell line to compensate for its defective mitochondrial function [50]. 1 H-NMR spectroscopy has been used to show that oxidative stress alters the metabolic prowww.e-enm.org 623 file in thyroid cancer, with increases in lactate and aromatic amino acids and a decrease in citrate [51].…”