Steroid receptor coactivator-3 as a target for anaplastic thyroid cancer

Endocr Relat Cancer. 2020 Apr;27(4):209-220. doi: 10.1530/ERC-19-0482.

Abstract

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy without effective therapeutic options to improve survival. Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator whose amplification and/or overexpression has been identified in many cancers. In this study, we explored the expression of SRC-3 in ATCs and the effects of a new class of SRC-3 inhibitor-2 (SI-2) in human ATC cells (THJ-11T and THJ-16T cells) and mouse xenograft models to assess therapeutic potential of SI-2 for the treatment of ATC. SRC-3 protein abundance was significantly higher in human ATC tissue samples and ATC cells than in differentiated thyroid carcinomas or normal controls. SI-2 treatment effectively reduced the SRC-3 expression in both ATC cells and ATC xenograft tumors induced by these cells. Cancer cell survival in ATC cells and tumor growth in xenograft tumors were significantly reduced by SI-2 treatment through induction of cancer cell apoptosis and cell cycle arrest. SI-2 also reduced cancer stem-like cells as shown by an inhibition of tumorsphere formation, ALDH activity, and expression of stem cell markers in ATC. These findings indicate that SRC-3 is a potential therapeutic target for treatment of ATC patients and that SI-2 is a potent and promising candidate for a new therapeutic agent.

Keywords: SI-2; anaplastic thyroid carcinoma; cancer stem-like cells; small-molecule inhibitor; steroid receptor coactivator-3.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / pathology
  • Nuclear Receptor Coactivator 3 / metabolism*
  • Thyroid Carcinoma, Anaplastic
  • Xenograft Model Antitumor Assays

Substances

  • Nuclear Receptor Coactivator 3