Abstract
The Wnt pathway is essential for stem cell maintenance, but little is known about its role in thyroid hormone signaling and thyroid stem cell survival and maintenance. In addition, the role of Wnt signaling in thyroid cancer progenitor cells is also unclear. Here, we present emerging evidence for the role of Wnt signaling in somatic thyroid stem cell and thyroid cancer stem cell function. An improved understanding of the role of Wnt signaling in thyroid physiology and carcinogenesis is essential for improving both thyroid disease diagnostics and therapeutics.
Highlights
Somatic stem cells are necessary for homeostasis across a variety of tissues
Wnt signaling was not required for thyroid progenitor cell specification, their mRNA expression profiles were consistent with Wnt pathway activation; this upregulation implies a critical, but currently undefined, role of Wnt signaling in thyroid stem cell biology
The role of Wnt signaling in thyroid cancer cell growth was confirmed by the demonstration that short hairpin RNA-mediated silencing of β-catenin resulted in decreased proliferation and promotion of cellular senescence as measured by an increase in β-galactosidase activity [69]
Summary
Somatic (adult) stem cells are necessary for homeostasis across a variety of tissues. Among the best-characterized examples are the gastrointestinal tract, where there is rapid turnover of the epithelium [1,2], and hematopoietic tissues, which have a strong capacity to regenerate that is dependent on the presence of long-term somatic stem cells [3]. Artificial thyroid hormone replacement with levothyroxine is the standard of care for hypothyroidism Despite this treatment, individuals with such thyroid dysfunction suffer from imbalances in cell metabolism, which can affect many important tissues throughout the body, including skin, bones, brain, and intestine. Thyroid hormone (TH) plays a role in many cellular functions, including proliferation, growth, differentiation, metabolism, regeneration, and homeostasis It is produced by the thyroid gland and travels through the bloodstream to regulate gene transcription at diverse sites. We discuss the future directions for defining the role of the Wnt pathway in thyroid stem cell research and the important questions that remain to be answered
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