title: Autophagy and thyroid carcinogenesis: genetic and epigenetic links.
abstract: Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, the treatment of radio-resistant papillary-type, of undifferentiated anaplastic, and of medullary-type thyroid cancers remains unsatisfactory. Autophagy is a vesicular process for the lysosomal degradation of protein aggregates and of damaged or redundant organelles. Autophagy plays an important role in cell homeostasis, and there is evidence that this process is dysregulated in cancer cells. Recent in vitro preclinical studies have indicated that autophagy is involved in the cytotoxic response to chemotherapeutics in thyroid cancer cells. Indeed, several oncogenes and oncosuppressor genes implicated in thyroid carcinogenesis also play a role in the regulation of autophagy. In addition, some epigenetic modulators involved in thyroid carcinogenesis also influence autophagy. In this review, we highlight the genetic and epigenetic factors that mechanistically link thyroid carcinogenesis and autophagy, thus substantiating the rationale for an autophagy-targeted therapy of aggressive and radio-chemo-resistant thyroid cancers.
authors.affiliation: Laboratory of Molecular Pathology, Department of Health SciencesUnit of Clinical Endocrinology Unit of Oncology, Department of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Morani
authors.forename: Rossella
authors.initials: R
authors.lastname: Titone
authors.forename: Loredana
authors.initials: L
authors.lastname: Pagano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galetto
authors.forename: Oscar
authors.initials: O
authors.lastname: Alabiso
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aimaretti
authors.forename: Ciro
authors.initials: C
authors.lastname: Isidoro
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009857:Oncogenes; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
keywords: autophagy; epigenetics; microRNA; oncogenes; thyroid cancer