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Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Steroid receptor coactivator-3 as a target for anaplastic thyroid cancer

Woo Kyung Lee1, Won Gu Kim1,2, Laura Fozzatti1,3

  • 1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Endocrine-Related Cancer
|January 25, 2020
PubMed

Insights

Steroid receptor coactivator-3 (SRC-3) is overexpressed in aggressive anaplastic thyroid carcinoma (ATC). A new inhibitor, SI-2, effectively reduced SRC-3, suppressed tumor growth, and induced apoptosis, showing therapeutic promise for ATC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with limited treatment options.
  • Steroid receptor coactivator-3 (SRC-3) is implicated in various cancers.
  • SRC-3's role in ATC pathogenesis and its therapeutic targeting remain underexplored.

Purpose of the Study:

  • To investigate SRC-3 expression in ATC.
  • To evaluate the therapeutic potential of a novel SRC-3 inhibitor, SI-2, in ATC models.
  • To assess SI-2's effects on cancer cell survival, tumor growth, and cancer stem-like cells in ATC.

Main Methods:

  • Quantitative analysis of SRC-3 protein levels in human ATC tissues and cell lines.
  • In vitro studies using human ATC cell lines (THJ-11T, THJ-16T) treated with SI-2.
  • In vivo studies using mouse xenograft models of human ATC treated with SI-2.
  • Assessment of apoptosis, cell cycle arrest, tumorsphere formation, ALDH activity, and stem cell marker expression.

Main Results:

  • SRC-3 protein was significantly overexpressed in ATC tissues and cells compared to controls.
  • SI-2 treatment markedly reduced SRC-3 expression in ATC cells and xenograft tumors.
  • SI-2 significantly inhibited ATC cell survival and tumor growth by inducing apoptosis and cell cycle arrest.
  • SI-2 demonstrated efficacy in reducing cancer stem-like cell populations in ATC.

Conclusions:

  • SRC-3 is a validated therapeutic target in anaplastic thyroid carcinoma.
  • The SRC-3 inhibitor SI-2 exhibits potent anti-cancer activity against ATC in preclinical models.
  • SI-2 represents a promising novel therapeutic candidate for the treatment of anaplastic thyroid carcinoma.
Keywords:
SI-2anaplastic thyroid carcinomacancer stem-like cellssmall-molecule inhibitorsteroid receptor coactivator-3

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