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

in Endocrine-Related Cancer
Authors:
Woo Kyung Lee Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Won Gu Kim Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

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Laura Fozzatti Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Sunmi Park Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Li Zhao Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Mark C Willingham Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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David Lonard Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Bert W O’Malley Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Sheue-yann Cheng Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Correspondence should be addressed to S Cheng: chengs@mail.nih.gov
DOI:
https://doi.org/10.1530/ERC-19-0482
Volume/Issue:
Volume 27: Issue 4
Article Type:
Research Article
Page Range:
209–220
Online Publication Date:
Apr 2020
Copyright:
© 2020 Society for Endocrinology 2020
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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.

Supplementary Materials

    • Table S1. Kegg Gene Sets Enriched in Tumors with Top 30 NCOA3 Expression Analyzed by Gene Set Enrichment Analysis in TCGA-THCA (versus Tumors with Bottom 30 NCOA3 Expression).
    • Table S2. Hallmark Gene Sets Enriched in Tumors with Top 30 NCOA3 Expression Analyzed by Gene Set Enrichment Analysis in TCGA-THCA (versus Tumors with Bottom 30 NCOA3 Expression).
    • Table S3. GSEA Results for Kegg or Hallmark Gene Sets in Tumors with Bottom 30 NCOA3 Expression in TCGA-THCA (versus Tumors with Top 30 NCOA3 Expression).
    • Reference Table I. Kegg or Hallmark Gene Sets Enriched in Tumors with Top Quartile NCOA3 Expression Analyzed by Gene Set Enrichment Analysis in TCGA-THCA (versus Tumors with Low Quartile NCOA3 Expression; n = 125, respectively).
    • Supplementary Fig. 1
    • Supplementary Fig. 2

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
12
Received Date:
22 Jan 2020
Accepted Date:
24 Jan 2020
Print Publication Date:
01 Apr 2020
Online Publication Date:
Apr 2020
Keywords:
anaplastic thyroid carcinoma; steroid receptor coactivator-3; small-molecule inhibitor; cancer stem-like cells; SI-2

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