Metabolic Reprogramming in Thyroid Cancer Cells

Thyroid cancer cells undergo profound metabolic reprogramming to support rapid proliferation, survival under stress and metastatic spread. A hallmark of this reprogramming is the shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, known as the Warburg effect, which favours rapid ATP generation and supplies biosynthetic precursors. Concurrently, enhanced glutaminolysis provides carbon and nitrogen for nucleotide and amino acid synthesis, while de novo lipid synthesis underpins membrane biogenesis. These alterations are orchestrated by oncogenic drivers such as mutant BRAF, aberrant PI3K-Akt signalling, stabilised HIF-1α and deregulated c-Myc, together with loss of tumour suppressors including p53 and PTEN. Metabolic changes also modify the tumour microenvironment, promoting acidification, immune evasion and stromal support. As a result, metabolic vulnerabilities have emerged as promising targets for novel diagnostic imaging agents and selective inhibitors, offering routes to overcome radioiodine resistance and improve outcomes in aggressive or refractory thyroid cancers.

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Metabolic Reprogramming in Thyroid Cancer Cells publication trend

The graph below shows the total number of articles in metabolic reprogramming in thyroid cancer cells across all publications each year (not limited to Nature Index journals).

Technical terms

Warburg effect: The preference of cancer cells for aerobic glycolysis over oxidative phosphorylation, resulting in increased lactate production despite sufficient oxygen.

Glycolysis: A metabolic pathway converting glucose to pyruvate, yielding ATP and NADH; often upregulated in cancer cells.

Glutaminolysis: The catabolism of glutamine into intermediates that feed the tricarboxylic acid cycle and support biosynthesis in tumour cells.

Oxidative phosphorylation: The mitochondrial process of ATP generation via electron transport and chemiosmotic coupling, typically downregulated in reprogrammed cancer cells.

Tumour microenvironment (TME): The complex milieu of stromal cells, immune infiltrates, extracellular matrix and metabolites that interact dynamically with cancer cells.

Metabolic reprogramming: The collective alteration of cellular metabolic pathways enabling cancer cells to meet energetic, biosynthetic and redox demands for growth and survival.

References

1. The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer. Journal of Translational Medicine (2023).
2. Reprogramming of Cellular Metabolism and Its Therapeutic Applications in Thyroid Cancer. Metabolites (2022).
3. Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment. Frontiers in Oncology (2021).