Evidence map›Paper›PMID 32796891›Full record

ArticleScientific reports2020

Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance.

Nitika, Jacob S Blackman, Laura E Knighton, Jade E Takakuwa, Stuart K Calderwood, Andrew W Truman

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. DNAJA: emerging targets for anti-tumor therapy.Future oncology (London, England) · 2025
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  14. HSP70 and their co-chaperones in the human malaria parasiteFrontiers in molecular biosciences · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

NitikaDepartment of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA.
Jacob S BlackmanDepartment of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA.
Laura E KnightonDepartment of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA.
Jade E TakakuwaDepartment of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA.
Stuart K CalderwoodDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.
Andrew W TrumanDepartment of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA. atruman1@uncc.edu.
University of North Carolina at Charlotte · USHarvard University · US

Funding

Understanding the reciprocal regulation between Hsp70 and the DNA damage response.R01GM139885 · NIGMS · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · PI TRUMAN, ANDREW WILLIAM · 2021 to 2024
$1.4M
Regulation of Hsp70-Mediated Cyclin D1 Destruction in Breast CancerR15CA208773 · NCI · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · PI TRUMAN, ANDREW WILLIAM · 2017 to 2017
$440k
NCI NIH HHS R15 CA208773NIH HHS R15CA208773
6 · The paper itself

Abstract

Heat shock protein 70 (Hsp70) is an important molecular chaperone that regulates oncoprotein stability and tumorigenesis. However, attempts to develop anti-chaperone drugs targeting molecules such as Hsp70 have been hampered by toxicity issues. Hsp70 is regulated by a suite of co-chaperone molecules that bring "clients" to the primary chaperone for efficient folding. Rather than targeting Hsp70 itself, here we have examined the feasibility of inhibiting the Hsp70 co-chaperone DNAJA1 as a novel anticancer strategy. We found DNAJA1 to be upregulated in a variety of cancers, suggesting a role in malignancy. To confirm this role, we screened the NIH Approved Oncology collection for chemical-genetic interactions with loss of DNAJA1 in cancer. 41 compounds showed strong synergy with DNAJA1 loss, whereas 18 dramatically lost potency. Several hits were validated using a DNAJA1 inhibitor (116-9e) in castration-resistant prostate cancer cell (CRPC) and spheroid models. Taken together, these results confirm that DNAJA1 is a hub for anticancer drug resistance and that DNAJA1 inhibition is a potent strategy to sensitize cancer cells to current and future therapeutics. The large change in drug efficacy linked to DNAJA1 suggests a personalized medicine approach where tumor DNAJA1 status may be used to optimize therapeutic strategy.

Indexed as

HSP40 Heat-Shock ProteinsHSP70 Heat-Shock ProteinsMolecular ChaperonesAntineoplastic AgentsCarcinogenesisDrug Resistance, NeoplasmHumansMolecular Targeted TherapyNeoplasmsOncogene ProteinsPrecision MedicineTumor Cells, CulturedAntineoplastic AgentsDNAJA1 protein, humanHSP40 Heat-Shock ProteinsHSP70 Heat-Shock ProteinsMolecular ChaperonesOncogene Proteins

Identifiers

PMID32796891
PMCPMC7429498
OpenAlexW3049454725

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.