Evidence map›Paper›PMID 32747423›Full record

ArticleMolecular cancer therapeutics2020

Hypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.

Joy M Gary, John K Simmons, Jinfei Xu, Shuling Zhang, Tyler J Peat, Nicholas Watson, Benjamin J Gamache, Ke Zhang, Alexander L Kovalchuk, Aleksandra M Michalowski and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. CRISPR-Cas knockout of miR21 reduces glioma growth.Molecular therapy oncolytics · 2022
    Article
  5. Article
  6. Article
  7. Review
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

19 authors at 5 institutions in 2 countries.

Joy M Gary *Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
John K Simmons *Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Jinfei Xu *Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Shuling ZhangLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Tyler J PeatLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Nicholas WatsonLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Benjamin J GamacheLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Ke ZhangLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Alexander L KovalchukLaboratory of Immunogenetics, NIAID, NIH, Rockville, Maryland.
Aleksandra M MichalowskiLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.ORCID 0000-0001-9259-6101
Jin-Qiu ChenLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Tuddow ThaiwongPathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan.
Matti KiupelPathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan.ORCID 0000-0003-4429-9529
Snehal GaikwadLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Maudeline EtienneLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
R Mark SimpsonLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Wendy DuboisLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland.
Joseph R TestaCancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania. mockb@mail.nih.gov joseph.testa@fccc.edu.ORCID 0000-0003-1301-5175
Beverly A MockLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, Maryland. mockb@mail.nih.gov joseph.testa@fccc.edu.ORCID 0000-0003-2479-4549
Center for Cancer Research · USFox Chase Cancer Center · USMichigan State University · USAmerican University · USImmungenetics (Germany) · DE

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
Preclinical Testing of HDAC, mTOR and MYC InhibitorsZIABC011065 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MOCK, BEVERLY · 2009 to 2025
$10.6M
The Genetics of Susceptibility to Mouse Plasma Cell TumorsZIABC010008 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MOCK, BEVERLY · 2009 to 2025
$9.0M
Basis for Lymphomagenesis in Akt2 Transgenic MiceR01CA077429 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI TESTA, JOSEPH R. · 1998 to 2013
$4.7M
A Modifier of Plasmacytoma Susceptibility Maps to Mouse Chr 1ZIABC011064 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MOCK, BEVERLY · 2009 to 2024
$2.4M
THE GENETICS OF SUSCEPTIBILITY TO MOUSE PLASMA CELL TUMORSZ01BC010008 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MOCK, BEVERLY A. · 1996 to 2008
$1.7M
Intramural NIH HHS Z01 BC010008Intramural NIH HHS ZIA BC010008Intramural NIH HHS ZIA BC011064Intramural NIH HHS ZIA BC011065NCI NIH HHS P30 CA006927NCI NIH HHS R01 CA077429
6 · The paper itself

Abstract

PI3K/AKT/mTOR pathway hyperactivation is frequent in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). To model inhibition of mTOR, pre-T-cell lymphoblastic leukemia/lymphoma (pre-T LBL) tumor development was monitored in mice with T lymphocyte-specific, constitutively active AKT (Lck-MyrAkt2) that were either crossed to mTOR knockdown (KD) mice or treated with the mTOR inhibitor everolimus. Lck-MyrAkt2;mTOR KD mice lived significantly longer than Lck-MyrAkt2;mTOR wild-type (WT) mice, although both groups ultimately developed thymic pre-T LBL. An increase in survival was also observed when Lck-MyrAkt2;mTOR WT mice were treated for 8 weeks with everolimus. The transcriptional profiles of WT and KD thymic lymphomas were compared, and Ingenuity Pathway Upstream Regulator Analysis of differentially expressed genes in tumors from mTOR WT versus KD mice identified let-7 and miR-21 as potential regulatory genes. mTOR KD mice had higher levels of let-7a and miR-21 than mTOR WT mice, and rapamycin induced their expression in mTOR WT cells. CDK6 was one of the most downregulated targets of both let-7 and miR21 in mTOR KD tumors. CDK6 overexpression and decreased expression of let-7 in mTOR KD cells rescued a G

Indexed as

AnimalsCarcinogenesisCyclin-Dependent Kinase 6Down-RegulationGene Expression ProfilingMiceMice, TransgenicTOR Serine-Threonine KinasesCDK6 protein, humanCyclin-Dependent Kinase 6MTOR protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID32747423
PMCPMC9574474
OpenAlexW3046574270

What Socratic 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 Socratic graph.