Evidence map›Paper›PMID 26542767›Full record

ArticleSurgery2016

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

Peter T White, Chitra Subramanian, Qing Zhu, Huaping Zhang, Huiping Zhao, Robert Gallagher, Barbara N Timmermann, Brian S J Blagg, Mark S Cohen

Abstract read
In one paragraph

Article in Surgery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Molecular Chaperones and Thyroid Cancer.International journal of molecular sciences · 2021
    Review
  11. Article
  12. Review
  13. The Potential of Metabolomics in the Diagnosis of Thyroid Cancer.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Peter T WhiteDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Chitra SubramanianDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Qing ZhuDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Huaping ZhangDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KS.
Huiping ZhaoDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KS.
Robert GallagherDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KS.
Barbara N TimmermannDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KS.
Brian S J BlaggDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KS.
Mark S CohenDepartment of Surgery, University of Michigan, Ann Arbor, MI. Electronic address: cohenmar@med.umich.edu.
University of Kansas · USUniversity of Michigan–Ann Arbor · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
WEIGHT CONTROL, CELL SIGNALING AND CANCER PREVENTIONP20RR015563 · NCRR · UNIVERSITY OF KANSAS LAWRENCE · PI ZUFFEREY, RACHEL · 2000 to 2009
$20.1M
University of Michigan Surgical Oncology Research Training ProgramT32CA009672 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JACQUELINE SARA JERUSS, WEIPING ZOU · 1991 to 2026
$6.0M
Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors`U01CA120458 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI BLAGG, BRIAN S J · 2007 to 2014
$2.6M
Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors`R01CA120458 · NCI · UNIVERSITY OF NOTRE DAME · PI BLAGG, BRIAN S J · 2006 to 2019
$1.9M
Biomaterials for treatment of head and neck cancerR01CA173292 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI FORREST, MARCUS LAIRD · 2013 to 2017
$1.4M
Avance II 500 High Performance Digital NMR Spectrometer SystemS10RR024664 · NCRR · UNIVERSITY OF KANSAS LAWRENCE · PI VANDERVELDE, DAVID G · 2007 to 2007
$468k
400 MHZ NUCLEAR MAGNETIC RESONANCE SPECTROMETERS10RR014767 · NCRR · UNIVERSITY OF KANSAS LAWRENCE · PI VANDERVELDE, DAVID G · 2001 to 2001
$346k
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA120458NCI NIH HHS R01 CA173292NCI NIH HHS T32 CA009672NCI NIH HHS U01 CA120458NCRR NIH HHS P20 RR015563NCRR NIH HHS S10 RR014767NCRR NIH HHS S10 RR024664NCRR NIH HHS S10RR024664
6 · The paper itself

Abstract

backgroundThyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion.

methodsValidated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers.

resultsWGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients β-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively.

conclusionKU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo.

Indexed as

Anticarcinogenic AgentsCell Line, TumorCell MovementCell ProliferationHSP90 Heat-Shock ProteinsHumansNeoplasm InvasivenessNeoplastic Stem CellsThyroid GlandThyroid NeoplasmsAnticarcinogenic AgentsHSP90 Heat-Shock Proteins

Identifiers

PMID26542767
PMCPMC4709031
OpenAlexW2189920580

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.