Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as a context-dependent tumor suppressor

A. Abols (Coresponding Author), K. Ducena, D. Andrejeva, L. Sadovska, E. Zandberga, J. Vilmanis, Z. Narbuts, J. Tars, J. Eglitis, V. Pirags, A. Line

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Trefoil factor 3 (TFF3) is overexpressed in a variety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the S phase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as a tumor suppressor or an oncogene depending on the cellular context.

Original languageEnglish
Pages (from-to)914-924
Number of pages11
JournalNeoplasma
Volume62
Issue number6
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Estrogen signaling
  • Follicular cells
  • Thyroid cancer

Field of Science

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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