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Cited by 43Wnt/β-catenin signaling in development and cancerThyroid Disorders and TreatmentsThyroid Cancer Diagnosis and Treatment

Wnt-independent role of β-catenin in thyroid cell proliferation and differentiation

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Sastre-Perona, Ana, Santisteban, Pilar·2014·Molecular Endocrinology
DOI 10.1210/me.2013-1377PMC PMC5414850
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Abstract

The Wnt/β-catenin pathway has been associated with thyroid cell growth and tumorigenesis. However, little is known regarding its involvement in the response to the key regulators of thyroid cell proliferation and differentiation. Here we show that TSH and IGF-1 increase β-catenin nuclear accumulation and its transcriptional activity in differentiated thyroid cells. This effect takes place in a Wnt-independent manner because TSH and IGF-1, through the activation of protein kinase A and protein kinase B/Akt, phosphorylate β-catenin at S552 and S675, which results in β-catenin release from E-cadherin at the adherens junctions. Nuclear β-catenin regulates thyroid cell proliferation, because its silencing or the overexpression of a dominant-negative form of T-cell factor 4 resulted in reduced levels of cyclin D1 and DNA synthesis. Furthermore, the β-catenin silencing markedly reduced the expression of Pax8, the main transcription factor involved in epithelial thyroid cell differentiation. Finally, we observed that β-catenin physically interacts with the transcription factor Pax8, increasing its transcriptional activity on the sodium iodide symporter (NIS) gene, a critical gene required for thyroid cell physiology. Taken together, our findings show that β-catenin plays a not yet described role in thyroid function including a functional interaction with Pax8.

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  • TSH can stimulate PAX8 mRNA and protein expression, likely via the CREB binding sites in the PAX8 gene promoter, as demonstrated in PCCl3 and FRTL-5 cells.

    “TSH can stimulate PAX8 mRNA and protein expression, likely via the CREB binding sites in the PAX8 gene promoter, as demonstrated in PCCl3 and FRTL-5 cells (144, 153).”

    From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [144]

    The Results report TSH-responsive Pax8 expression in PCCl3 cells, and the Discussion says CREB binding sites in the Pax8 promoter help explain TSH/cAMP regulation. However, the reported Pax8 protein increase was observed with an active β-catenin mutant, not explicitly attributed to TSH; the FRTL5 experiments reproduced β-catenin responses, not the claimed Pax8 mRNA and protein response. (LLM, conf=0.86)

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Authors
Sastre-Perona, A., & Santisteban, P.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
Santisteban, Pilar
ORCID
Venue
Molecular Endocrinology
Publisher
The Endocrine Society
Published
2014-05-01
Volume
28
Issue
5
Pages
681-695
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
DOI
10.1210/me.2013-1377
PMC
PMC5414850
OpenAlex
W2115293639
Cited by
43
References
0
Citations by year
2026: 1 · 2025: 3 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 4
FWCI
1.89
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
β-catenin, thyroid cell proliferation, thyroid cell differentiation, thyroid-stimulating hormone, insulin-like growth factor I, protein kinase A, Akt, β-catenin phosphorylation, E-cadherin, adherens junctions, TCF4, cyclin D1, PAX8, sodium iodide symporter, transcriptional regulation
MeSH terms
PAX8 Transcription Factor, Animals, Cell Differentiation, Cell Line, Insulin-Like Growth Factor I, Rats, Inbred F344, Thyroid Gland, Thyrotropin, Transcriptional Activation, Cyclin D1, Active Transport, Cell Nucleus, Cell Proliferation, beta Catenin, Paired Box Transcription Factors, Wnt Signaling Pathway

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