Thyroid Cancer and Circadian Clock Disruption

SIMPLE SUMMARY: In this manuscript we review the recent literature supporting a biological link between circadian clock disruption and thyroid cancer development and progression. After a brief description of the involvement of the circadian clock machinery in the cell cycle, stemness and cancer, we discuss the scientific evidence supporting the contribution of circadian clockwork dysfunction in thyroid tumorigenesis and the possible molecular mechanisms underlying this relationship. We also point out the potential clinical implications of this link highlighting its impact on thyroid cancer prevention, diagnosis and therapy. ABSTRACT: Thyroid cancer (TC) represents the most common malignancy of the endocrine system, with an increased incidence across continents attributable to both improvement of diagnostic procedures and environmental factors. Among the modifiable risk factors, insulin resistance might influence the development of TC. A relationship between circadian clock machinery disfunction and TC has recently been proposed. The circadian clock machinery comprises a set of rhythmically expressed genes responsible for circadian rhythms. Perturbation of this system contributes to the development of pathological states such as cancer. Several clock genes have been found deregulated upon thyroid nodule malignant transformation. The molecular mechanisms linking circadian clock disruption and TC are still unknown but could include insulin resistance. Circadian misalignment occurring during shift work, jet lag, high fat food intake, is associated with increased insulin resistance. This metabolic alteration, in turn, is associated with a well-known risk factor for TC i.e., hyperthyrotropinemia, which could also be induced by sleep disturbances. In this review, we describe the mechanisms controlling the circadian clock function and its involvement in the cell cycle, stemness and cancer. Moreover, we discuss the evidence supporting the link between circadian clockwork disruption and TC development/progression, highlighting its potential implications for TC prevention, diagnosis and therapy.