title: Thyroid Hormone, Cancer, and Apoptosis.
abstract: Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016.
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.|PhD program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Tan
authors.initials: YT
authors.lastname: Chin
authors.affiliation: Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chen S H
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Husan-Yu
authors.initials: HY
authors.lastname: Lai
authors.affiliation: Center of Excellence Cancer Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wang-Peng
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Leory F
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Heng-Yuan
authors.initials: HY
authors.lastname: Tang
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.|Albany Medical College, Albany, New York, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004067:Digestive System Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones