Abstract
Approximately 90% of non-medullary thyroid malignancies originate from the follicular cell and are classified as papillary or follicular (well-differentiated) thyroid carcinomas, showing an overall favourable prognosis. However, recurrence or persistence of the disease occurs in some cases associated with the presence of loco-regional or distant metastatic lesions that generally become resistant to radioiodine therapy, while glucose uptake and metabolism are increased. Recent advances in the field of tumor progression have shown that CTC (circulating tumour cells) are metabolic and genetically heterogeneous. There is now special interest in unravelling the mechanisms that allow the reminiscence of dormant tumour lesions that might be related to late disease progression and increased risk of recurrence. AMPK (AMP-activated protein kinase) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism that are fundamental for cell survival in a stressful environment; nevertheless, the activation of this kinase also decreases cell proliferation rate and induces tumour cell apoptosis. In the thyroid field, AMPK emerged as a novel important intracellular pathway, since it regulates both iodide and glucose uptakes in normal thyroid cells. Furthermore, it has recently been demonstrated that the AMPK pathway is highly activated in papillary thyroid carcinomas, although the clinical significance of these findings remains elusive. Herein we review the current knowledge about the role of AMPK activation in thyroid physiology and pathophysiology, with special focus on thyroid cancer.
Highlights
Palpable and non-palpable thyroid nodules are common endocrine tumours that can be detected in as much as 70 % of a population if sensitive image-assisted examination methods are used [1]
Nodular lesions are frequent in the overall population, only 5–10 % of thyroid nodules correspond to malignant lesions, and thyroid carcinoma is a rare disease that accounts for just 1 % of all human cancers, it is the most common endocrine malignancy [1,3]
We have recently shown that the expression and activity of AMP-activated protein kinase (AMPK) is increased in papillary thyroid carcinoma [21]
Summary
Palpable and non-palpable thyroid nodules are common endocrine tumours that can be detected in as much as 70 % of a population if sensitive image-assisted examination methods are used [1]. In the past 10 years, risk stratification systems were reported in order to try to better establish the adequate intervention for each patient [13,14]. In this context, the serum levels of thyroglobulin, anti-thyroglobulin and the identification of structural disease by traditional tomography, scintigraphy with 131I-radioiodide and 18F-FDG-PET (18F-fluoro-deoxiglucose positron emission tomography) are very important criteria for assessment of recurrent or persistent disease. We described that the energy sensor AMPK (AMP-activated protein kinase) plays an important physiological role in the thyroid gland by regulating both iodide and glucose uptakes [18,19]. We focused on the current knowledge about NIS regulation by AMPK in thyroid cells and the possible involvement of AMPK signalling pathway in thyroid cancer cell biology
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