Evidence map›Paper›PMID 28504649›Full record

ArticleThe Journal of clinical investigation2017

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth.

Jaya Sangodkar, Abbey Perl, Rita Tohme, Janna Kiselar, David B Kastrinsky, Nilesh Zaware, Sudeh Izadmehr, Sahar Mazhar, Danica D Wiredja, Caitlin M O'Connor and 35 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed
9.7field-weighted citation impact, top 1% 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

130 citing papers in PubMed, 197 citations in OpenAlex.

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70 more citing papers are in PubMed but not listed here.

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

45 authors at 8 institutions in 3 countries.

Jaya SangodkarIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Abbey PerlCase Western Reserve University, Cleveland, Ohio, USA.
Rita TohmeCase Western Reserve University, Cleveland, Ohio, USA.
Janna KiselarCase Western Reserve University, Cleveland, Ohio, USA.
David B KastrinskyIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Nilesh ZawareIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Sudeh IzadmehrIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Sahar MazharCase Western Reserve University, Cleveland, Ohio, USA.
Danica D WiredjaCase Western Reserve University, Cleveland, Ohio, USA.
Caitlin M O'ConnorCase Western Reserve University, Cleveland, Ohio, USA.
Divya HoonIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Neil S DhawanIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Daniela SchlatzerCase Western Reserve University, Cleveland, Ohio, USA.
Shen YaoIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Daniel LeonardCase Western Reserve University, Cleveland, Ohio, USA.
Alain C BorczukWeill Cornell Medical College, New York, New York, USA.
Giridharan GokulranganCase Western Reserve University, Cleveland, Ohio, USA.
Lifu WangUniversity of Virginia, Charlottesville, Virginia, USA.
Elena SvensonCase Western Reserve University, Cleveland, Ohio, USA.
Caroline C FarringtonCase Western Reserve University, Cleveland, Ohio, USA.
Eric YuanCase Western Reserve University, Cleveland, Ohio, USA.
Rita A AvelarCase Western Reserve University, Cleveland, Ohio, USA.
Agnes StachnikIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Blake SmithIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Vickram GidwaniIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Heather M GianniniIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Daniel McQuaidIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Kimberly McClinchIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Zhizhi WangUniversity of Washington, Seattle, Washington, USA.
Alice C LevineIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Rosalie C SearsOregon Health & Science University, Portland, Oregon, USA.
Edward Y ChenIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Qiaonan DuanIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Manish DattInternational Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Shozeb HaiderSchool of Pharmacy, University College London, London, United Kingdom.
Avi Ma'ayanIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Analisa DiFeoCase Western Reserve University, Cleveland, Ohio, USA.
Neelesh SharmaCase Western Reserve University, Cleveland, Ohio, USA.
Matthew D GalskyIcahn School of Medicine at Mount Sinai, New York, New York, USA.
David L BrautiganUniversity of Virginia, Charlottesville, Virginia, USA.
Yiannis A IoannouIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Wenqing XuUniversity of Washington, Seattle, Washington, USA.
Mark R ChanceCase Western Reserve University, Cleveland, Ohio, USA.
Michael OhlmeyerIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Goutham NarlaCase Western Reserve University, Cleveland, Ohio, USA.
Icahn School of Medicine at Mount Sinai · USCase Western Reserve University · USUniversity of Washington · USUniversity of Virginia · USCleveland Clinic Lerner College of Medicine · USCornell University · USInternational Centre for Genetic Engineering and Biotechnology · INOregon Health & Science University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Data Coordination and Integration Center for LINCS-BD2KU54HL127624 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MA'AYAN, AVI, SCHURER, STEPHAN C · 2014 to 2019
$23.5M
Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
NRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9M
The Role of post-translational activation of Myc in pancreatic cancerR01CA196228 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SEARS, ROSALIE C · 2015 to 2019
$2.0M
User Interface PortalU54CA189201 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DUDLEY, JOEL THOMAS, MA'AYAN, AVI · 2014 to 2017
$1.9M
Small Molecule Activators of PP2A (SMAPs) for Prostate Cancer TherapyR01CA181654 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NARLA, GOUTHAM · 2015 to 2019
$1.9M
Defining the role of the PR72 regulatory subunit in small molecule mediated activation of PP2A's tumor suppressive activityF31CA213554 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI PERL, ABBEY LEIGH · 2017 to 2018
$71k
NCATS NIH HHS TL1 TR002549NCI NIH HHS F31 CA213554NCI NIH HHS R01 CA181654NCI NIH HHS R01 CA196228NCI NIH HHS U54 CA189201NHLBI NIH HHS U54 HL127624NIBIB NIH HHS P30 EB009998NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDrug Resistance, NeoplasmEnzyme ActivationEnzyme ActivatorsHumansMaleMice, Inbred BALB CMice, NudeMice, TransgenicProtein BindingProtein Phosphatase 2Proto-Oncogene Proteins p21(ras)Signal TransductionAntineoplastic AgentsEnzyme ActivatorsKRAS protein, humanProtein Phosphatase 2Proto-Oncogene Proteins p21(ras)

Identifiers

PMID28504649
PMCPMC5451217
OpenAlexW2613638456

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.