Evidence map›Paper›PMID 34209460›Full record

ArticleBiomolecules2021

Credentialing and Pharmacologically Targeting PTP4A3 Phosphatase as a Molecular Target for Ovarian Cancer.

John S Lazo, Elizabeth R Sharlow, Robert Cornelison, Duncan J Hart, Danielle C Llaneza, Anna J Mendelson, Ettore J Rastelli, Nikhil R Tasker, Charles N Landen, Peter Wipf

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

John S LazoDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.ORCID 0000-0002-0645-4025
Elizabeth R SharlowDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Robert CornelisonDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Duncan J HartDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Danielle C LlanezaDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Anna J MendelsonDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Ettore J RastelliDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.ORCID 0000-0003-2778-7635
Nikhil R TaskerDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Charles N LandenDepartment of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA 22908, USA.
Peter WipfDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.ORCID 0000-0001-7693-5863
University of Virginia · USUniversity of Pittsburgh · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
Cancer Research Training Program: From Molecular Mechanisms to Therapeutic StrategiesT32CA009109 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Andrew Carl Dudley, Melanie R Rutkowski · 1985 to 2026
$13.9M
Operetta CLS High-content Imaging SystemS10OD021723 · OD · UNIVERSITY OF VIRGINIA · PI LAZO, JOHN S. · 2017 to 2017
$516k
Developing small molecule PTP4A3 inhibitors for ovarian cancerR43CA228774 · NCI · KEVIRX INC. · PI LAZO, JOHN S. · 2019 to 2019
$289k
Department of Defense BC170507NCI NIH HHS P30 CA044579NCI NIH HHS R43 CA228774NCI NIH HHS T32 CA009109NIH HHS GM131732NIH HHS P30 CA044579NIH HHS R43 CA228774NIH HHS S10 OD021723NIH HHS S10OD021723U.S. Department of Defense W81XWH-18-1-011Virginia Center for Innovative Technology SBIR20-12-LS
6 · The paper itself

Abstract

High grade serous ovarian cancer (OvCa) frequently becomes drug resistant and often recurs. Consequently, new drug targets and therapies are needed. Bioinformatics-based studies uncovered a relationship between high Protein Tyrosine Phosphatase of Regenerating Liver-3 (PRL3 also known as PTP4A3) expression and poor patient survival in both early and late stage OvCa. PTP4A3 mRNA levels were 5-20 fold higher in drug resistant or high grade serous OvCa cell lines compared to nonmalignant cells. JMS-053 is a potent allosteric small molecule PTP4A3 inhibitor and to explore further the role of PTP4A3 in OvCa, we synthesized and interrogated a series of JMS-053-based analogs in OvCa cell line-based phenotypic assays. While the JMS-053 analogs inhibit in vitro PTP4A3 enzyme activity, none were superior to JMS-053 in reducing high grade serous OvCa cell survival. Because PTP4A3 controls cell migration, we interrogated the effect of JMS-053 on this cancer-relevant process. Both JMS-053 and CRISPR/Cas9 PTP4A3 depletion blocked cell migration. The inhibition caused by JMS-053 required the presence of PTP4A3. JMS-053 caused additive or synergistic in vitro cytotoxicity when combined with paclitaxel and reduced in vivo OvCa dissemination. These results indicate the importance of PTP4A3 in OvCa and support further investigations of the lead inhibitor, JMS-053.

Indexed as

Cell Line, TumorCell MovementCell SurvivalDatabases, GeneticFemaleHumansIminesNeoplasm ProteinsOvarian NeoplasmsPhosphoric Monoester HydrolasesProtein Tyrosine PhosphatasesPyridinesIminesJMS-053Neoplasm ProteinsPhosphoric Monoester HydrolasesProtein Tyrosine PhosphatasesPTP4A3 protein, humanPyridinescell migrationdrug synergydrug target validationIL-6ovarian cancerprotein tyrosine phosphatase

Identifiers

PMID34209460
PMCPMC8329922
OpenAlexW3176468869

What OpenQuestion holds

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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.