Cited by 314Heat shock proteins researchCell death mechanisms and regulationUbiquitin and proteasome pathways

Dual Targeting of HSC70 and HSP72 Inhibits HSP90 Function and Induces Tumor-Specific Apoptosis

Open access
Powers, Marissa V., Clarke, Paul A., Workman, Paul·2008·Cancer Cell

Abstract

Heat-shock protein 70 (HSP70) isoforms contribute to tumorigenesis through their well-documented antiapoptotic activity and via their role as cochaperones for the HSP90 molecular chaperone. HSP70 expression is induced following treatment with HSP90 inhibitors, which may attenuate the cell death effects of this class of inhibitor. Here we show that silencing either heat-shock cognate 70 (HSC70) or HSP72 expression in human cancer cell lines has no effect on HSP90 activity or cell proliferation. However, simultaneously reducing the expression of both of these isoforms induces proteasome-dependent degradation of HSP90 client proteins, G1 cell-cycle arrest, and extensive tumor-specific apoptosis. Importantly, simultaneous silencing of HSP70 isoforms in nontumorigenic cell lines does not result in comparable growth arrest or induction of apoptosis, indicating a potential therapeutic window.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.ccr.2008.08.002

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Part of this paper’s reference list could not be split into single entries.

Flagged first, then by citations

4 of the 36 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Powers, M. V., Clarke, P. A., & Workman, P.
Affiliations
Institute of Cancer Research (GB)
Corresponding author
Workman, Paul
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2008-09
Volume
14
Issue
3
Pages
250-262
ISSN
1535-6108 (ISSN-L)
OpenAlex
W2170573493
Cited by
307
References
36
Citations by year
2026: 7 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 15 · 2020: 8 · 2019: 17 · 2018: 16 · 2017: 18 · 2016: 24 · 2015: 25 · 2014: 27 · 2013: 29 · 2012: 24
FWCI
10.38
Type
journal article
Language
en
Open access
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Cancer Research UK (C309/A8274, C309/A2187)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
Hsc70, HSP72, HSP90, Hsp90 inhibitors, proteasomal degradation, Hsp90 client proteins, G1 cell cycle arrest, heat shock proteins, cancer cell lines, therapeutic window, anti-apoptotic effects
MeSH terms
Bortezomib, Boronic Acids, Cell Cycle, Cell Line, Humans, Kinetics, Neoplasms, Poly(ADP-ribose) Polymerases, Protease Inhibitors, Pyrazines, Transfection, Benzoquinones, Apoptosis, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Proto-Oncogene Proteins c-raf, Protein Isoforms, RNA, Small Interfering, HCT116 Cells, Cell Line, Tumor, Proteasome Endopeptidase Complex, Lactams, Macrocyclic, Cell Proliferation, HSC70 Heat-Shock Proteins, HSP72 Heat-Shock Proteins, Cyclin-Dependent Kinase 4, Ubiquitination, Proteasome Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review