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Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion

Peter T White1, Chitra Subramanian1, Qing Zhu1

  • 1Department of Surgery, University of Michigan, Ann Arbor, MI.

Surgery
|November 7, 2015
PubMed
Abstract

Insights

Novel HSP90 inhibitors KU711 and WGA-TA effectively target thyroid cancer stem cells (CSCs). These agents inhibit CSC function, migration, and invasion in various thyroid cancer types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Thyroid cancer stem cells (CSCs) expressing ALDH and CD44 markers drive tumor progression.
  • Targeting CSCs is crucial for effective thyroid cancer treatment.

Purpose of the Study:

  • To evaluate the efficacy of novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG against thyroid CSCs.
  • To assess the impact of these inhibitors on CSC function, migration, and invasion.

Main Methods:

  • Treatment of human thyroid cancer cell lines (papillary, follicular, anaplastic) with three HSP90 inhibitors.
  • Quantification of CSCs using aldehyde dehydrogenase activity and CD44 expression.
  • Assessment of thyrosphere formation, protein pathway analysis, and cell migration/invasion assays.

Main Results:

  • KU711 and WGA-TA significantly reduced CD44 expression, ALDEFLOR activity, and sphere formation in thyroid cancer cells.
  • Both inhibitors markedly decreased cell migration and invasion.
  • WGA-TA demonstrated superior inhibition of HSP90 client proteins like β-catenin, BRAF, and Akt.

Conclusions:

  • KU711 and WGA-TA are potent novel HSP90 inhibitors that target thyroid CSCs.
  • These inhibitors effectively suppress CSC function, migration, and invasion in both differentiated and anaplastic thyroid cancers.
  • Further in vivo studies are warranted to explore their translational potential.

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