Thyroid hormone promotes differentiation of colon cancer stem cells

Mol Cell Endocrinol. 2017 Dec 25:459:84-89. doi: 10.1016/j.mce.2017.03.017. Epub 2017 Mar 22.

Abstract

Tumor formation and maintenance depend on a small fraction of cancer stem cells (CSCs) that can self-renew and generate a wide variety of differentiated cells. CSCs are resistant to chemotherapy and radiation, and can represent a reservoir of cancer cells that often cause relapse after treatment. Evidence suggests that CSCs also give rise to metastases. Thyroid hormone (TH) controls a variety of biological processes including the development and functioning of most adult tissues. Recent years has seen the emergence of an intimate link between TH and multiple steps of tumorigenesis. Thyroid hormone controls the balance between the proliferation and differentiation of CSCs, and may thus be a druggable anti-cancer agent. Here, we review current understanding of the effects of TH on colorectal CSCs, including the cross regulatory loops between TH and regulators of CSC stemness. Targeting TH in the tumor microenvironment may improve treatment strategies.

Keywords: Cancer stem cells; Deiodinases; Thyroid hormone.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Carcinogenesis / radiation effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / radiation effects
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Colon / radiation effects
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy
  • Gamma Rays / therapeutic use
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Iodide Peroxidase / genetics*
  • Iodide Peroxidase / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects
  • Receptors, Thyroid Hormone / genetics*
  • Receptors, Thyroid Hormone / metabolism
  • Signal Transduction
  • Thyroid Hormones / agonists
  • Thyroid Hormones / genetics*
  • Thyroid Hormones / metabolism
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / radiation effects

Substances

  • Antineoplastic Agents
  • Isoenzymes
  • Receptors, Thyroid Hormone
  • Thyroid Hormones
  • Iodide Peroxidase