Evidence map›Paper›PMID 27741517›Full record

ArticleOncotarget2016

Ral A, via activating the mitotic checkpoint, sensitizes cells lacking a functional Nf1 to apoptosis in the absence of protein kinase C.

Suthakar Ganapathy, Johan B Fagman, Ling Shen, Tianqi Yu, Xiaodong Zhou, Wei Dai, Alexandros Makriyannis, Changyan Chen

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. 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

8 authors at 4 institutions in 3 countries.

Suthakar GanapathyCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Johan B FagmanThe Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, SE.
Ling ShenCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Tianqi YuCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Xiaodong ZhouCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Wei DaiDepartment of Environmental Medicine, New York University, Tuxedo, NY, USA.
Alexandros MakriyannisCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Changyan ChenCenter for Drug Discovery, Northeastern University, Boston, MA, USA.
Northeastern University · USFirst Affiliated Hospital of Nanchang University · CNNew York University · USUniversity of Gothenburg · SE

Funding

Study of Ras-Mediated ApoptosisR01CA100498 · NCI · NORTHEASTERN UNIVERSITY · PI CHEN, CHANGYAN · 2004 to 2017
$2.5M
Study of Anti-Survival signals in NF1R01CA153354 · NCI · NORTHEASTERN UNIVERSITY · PI CHEN, CHANGYAN · 2012 to 2017
$1.6M
NCI NIH HHS R01 CA100498NCI NIH HHS R01 CA153354
6 · The paper itself

Abstract

Nf1 mutations or deletions are suggested to underlie the tumor predisposition of NF1 (neurofibromatosis type 1) and few treatments are available for treating NF1 patients with advanced malignant tumors. Aberrant activation of Ras in Nf1-deficient conditions is responsible for the promotion of tumorigenesis in NF1. PKC is proven to be an important factor in supporting the viability of Nf1-defected cells, but the molecular mechanisms are not fully understood. In this study, we demonstrate that the inhibition of protein kinase C (PKC) by 1-O-Hexadecyl-2-O-methyl-rac-glycerol (HMG, a PKC inhibitor) preferentially sensitizes Nf1-defected cells to apoptosis, via triggering a persistent mitotic arrest. In this process, Ral A is activated. Subsequently, Chk1 is phosphorylated and translocated to the nucleus. Silencing Ral A significantly blocks Chk1 nuclear translocation and releases HMG-treated Nf1-deficient cells from mitotic arrest, resulting in the reduction of the magnitude of apoptosis. Thus, our study reveals that PKC is able to maintain the homeostasis or viability of Nf1-defected cells and may serve as a potential target for developing new therapeutic strategies.

Indexed as

ApoptosisM Phase Cell Cycle CheckpointsActive Transport, Cell NucleusAnimalsCell LineCell Line, TumorCheckpoint Kinase 1Glyceryl EthersHumansMice, Inbred BALB CNerve Sheath NeoplasmsNeurofibromin 1PhosphorylationProtein Kinase Cral GTP-Binding ProteinsRNA Interference1-O-hexadecyl-2-O-methylglycerolCheckpoint Kinase 1Glyceryl EthersNeurofibromin 1Protein Kinase Cral GTP-Binding ProteinsapoptosisChk1mitotic catastropheNf1Ral A

Identifiers

PMID27741517
PMCPMC5356664
OpenAlexW2529960107

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.