Metabolic Reprogramming in Thyroid Cancer: Role of the Epithelial-Mesenchymal Transition

Thyroid cancer (TC) represents the most common endocrine malignancy, with an increasing incidence all over the world. Papillary TC (PTC), a differentiated TC subtype, is the most common and, even though it has an excellent prognosis following radioiodine (RAI) ablation, it shows an aggressive behavior in 20–30% of cases, becoming RAI-resistant and/or metastatic. On the other side, anaplastic thyroid carcinoma (ATC), the most undifferentiated TC, is a rare but devastating disease, indicating that progression of differentiated to undifferentiated forms of TC could be responsible for RAI-resistance and increased mortality. The epithelial-to-mesenchymal transition (EMT) plays a pivotal role in both tumor progression and resistance to therapy. Moreover, during tumor progression, cancer cells modify their metabolism to meet changed requirements for cellular proliferation. Through these metabolic changes, cancer cells may adopt cancer stem cell-like properties and express an EMT phenotype. EMT, in turn, can induce metabolic changes to which cancer cells become addicted. Here we review metabolic reprogramming in TC highlighting the role of EMT with the aim to explore a potential field to find out new therapeutic strategies for advanced-stage PTC. Accordingly, we discuss the identification of the metabolic enzymes and metabolites, critical to TC progression, which can be employed either as predicting biomarkers of tumor response to RAI therapy or possible targets in precision medicine.